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Sample records for irradiated normal tissues

  1. Oxygen delivery in irradiated normal tissue

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    Kiani, M.F.; Ansari, R. [Univ. of Tennessee Health Science Center, Memphis, TN (United States). School of Biomedical Engineering; Gaber, M.W. [St. Jude Children' s Research Hospital, Memphis, TN (United States)

    2003-03-01

    Ionizing radiation exposure significantly alters the structure and function of microvascular networks, which regulate delivery of oxygen to tissue. In this study we use a hamster cremaster muscle model to study changes in microvascular network parameters and use a mathematical model to study the effects of these observed structural and microhemodynamic changes in microvascular networks on oxygen delivery to the tissue. Our experimental observations indicate that in microvascular networks while some parameters are significantly affected by irradiation (e.g. red blood cell (RBC) transit time), others remain at the control level (e.g. RBC path length) up to 180 days post-irradiation. The results from our mathematical model indicate that tissue oxygenation patterns are significantly different in irradiated normal tissue as compared to age-matched controls and the differences are apparent as early as 3 days post irradiation. However, oxygen delivery to irradiated tissue was not found to be significantly different from age matched controls at any time between 7 days to 6 months post-irradiation. These findings indicate that microvascular late effects in irradiated normal tissue may be due to factors other than compromised tissue oxygenation. (author)

  2. Analytical formulae in fractionated irradiation of normal tissue

    International Nuclear Information System (INIS)

    Kozubek, S.

    1982-01-01

    The new conception of the modeling of the cell tissue kinetics after fractionated irradiation is proposed. The formulae given earlier are compared with experimental data on various normal tissues and further adjustments are considered. The tissues are shown to exhibit several general patterns of behaviour. The repopulation, if it takes place, seems to start after some time, independently of fractionation in first approximation and can be treated as simple autogenesis. The results are compared with the commonly used NSD conception and the well-known Cohen cell tissue kinetic model

  3. Accumulation of DNA Double-Strand Breaks in Normal Tissues After Fractionated Irradiation

    International Nuclear Information System (INIS)

    Ruebe, Claudia E.; Fricke, Andreas; Wendorf, Juliane; Stuetzel, Annika; Kuehne, Martin; Ong, Mei Fang; Lipp, Peter; Ruebe, Christian

    2010-01-01

    Purpose: There is increasing evidence that genetic factors regulating the recognition and/or repair of DNA double-strand breaks (DSBs) are responsible for differences in radiosensitivity among patients. Genetically defined DSB repair capacities are supposed to determine patients' individual susceptibility to develop adverse normal tissue reactions after radiotherapy. In a preclinical murine model, we analyzed the impact of different DSB repair capacities on the cumulative DNA damage in normal tissues during the course of fractionated irradiation. Material and Methods: Different strains of mice with defined genetic backgrounds (SCID -/- homozygous, ATM -/- homozygous, ATM +/- heterozygous, and ATM +/+ wild-type mice) were subjected to single (2 Gy) or fractionated irradiation (5 x 2 Gy). By enumerating γH2AX foci, the formation and rejoining of DSBs were analyzed in organs representative of both early-responding (small intestine) and late-responding tissues (lung, kidney, and heart). Results: In repair-deficient SCID -/- and ATM -/- homozygous mice, large proportions of radiation-induced DSBs remained unrepaired after each fraction, leading to the pronounced accumulation of residual DNA damage after fractionated irradiation, similarly visible in early- and late-responding tissues. The slight DSB repair impairment of ATM +/- heterozygous mice was not detectable after single-dose irradiation but resulted in a significant increase in unrepaired DSBs during the fractionated irradiation scheme. Conclusions: Radiation-induced DSBs accumulate similarly in acute- and late-responding tissues during fractionated irradiation, whereas the whole extent of residual DNA damage depends decisively on the underlying genetically defined DSB repair capacity. Moreover, our data indicate that even minor impairments in DSB repair lead to exceeding DNA damage accumulation during fractionated irradiation and thus may have a significant impact on normal tissue responses in clinical

  4. The effect of irradiation on function in self-renewing normal tissues with differing proliferative organisation

    International Nuclear Information System (INIS)

    Wheldon, T.E.; Michalowski, A.S.

    1982-01-01

    The primary effect of irradiation on self-renewing normal tissues is sterilisation of their proliferative cells, but how this translates into failure of tissue function depends on the mode of organisation of the tissue concerned. It has recently been suggested (Michalowski, 1981) that proliferative normal tissues may be classed as ''hierarchical'' (like haemopoietic tissues) or as ''flexible'' (like liver parenchyma) and that radiation injury to tissue function develops by different pathways in these tissues. Mathematical model studies confirm the different radiation responses of differently organized tissues. Tissues of the ''flexible'' or ''F-type'' category display a variety of novel radiobiological properties, different from those of the more familiar ''hierarchical'' or ''H-type'' tissues. The ''F-type'' responses are strongly influenced by radiation-sterilised (''doomed'') cells, and is is suggested that the role of ''doomed'' cells has been undervalued relative to that of clonogenic survivors. Since ''F-type'' tissues have characteristically low rates of cell renewal, it is possible that these tissues are preferentially responsible for late effects of irradiation in clinical radiotherapy. (author)

  5. ALK1 heterozygosity delays development of late normal tissue damage in the irradiated mouse kidney

    International Nuclear Information System (INIS)

    Scharpfenecker, Marion; Floot, Ben; Korlaar, Regina; Russell, Nicola S.; Stewart, Fiona A.

    2011-01-01

    Background and Purpose: Activin receptor-like kinase 1 (ALK1) is a transforming growth factor β (TGF-β) receptor, which is mainly expressed in endothelial cells regulating proliferation and migration in vitro and angiogenesis in vivo. Endothelial cells also express the co-receptor endoglin, which modulates ALK1 effects on endothelial cells. Our previous studies showed that mice with reduced endoglin levels develop less irradiation-induced vascular damage and fibrosis, caused by an impaired inflammatory response. This study was aimed at investigating the role of ALK1 in late radiation toxicity. Material and Methods: Kidneys of ALK +/+ and ALK1 +/- mice were irradiated with 14 Gy. Mice were sacrificed at 10, 20, and 30 weeks after irradiation and gene expression and protein levels were analyzed. Results: Compared to wild type littermates, ALK1 +/- mice developed less inflammation and fibrosis at 20 weeks after irradiation, but displayed an increase in pro-inflammatory and pro-fibrotic gene expression at 30 weeks. In addition, ALK1 +/- mice showed superior vascular integrity at 10 and 20 weeks after irradiation which deteriorated at 30 weeks coinciding with changes in the VEGF pathway. Conclusions: ALK1 +/- mice develop a delayed normal tissue response by modulating the inflammatory response and growth factor expression after irradiation.

  6. Tissue irradiator

    International Nuclear Information System (INIS)

    Hungate, F.P.; Riemath, W.F.; Bunnell, L.R.

    1975-01-01

    A tissue irradiator is provided for the in-vivo irradiation of body tissue. The irradiator comprises a radiation source material contained and completely encapsulated within vitreous carbon. An embodiment for use as an in-vivo blood irradiator comprises a cylindrical body having an axial bore therethrough. A radioisotope is contained within a first portion of vitreous carbon cylindrically surrounding the axial bore, and a containment portion of vitreous carbon surrounds the radioisotope containing portion, the two portions of vitreous carbon being integrally formed as a single unit. Connecting means are provided at each end of the cylindrical body to permit connections to blood-carrying vessels and to provide for passage of blood through the bore. In a preferred embodiment, the radioisotope is thulium-170 which is present in the irradiator in the form of thulium oxide. A method of producing the preferred blood irradiator is also provided, whereby nonradioactive thulium-169 is dispersed within a polyfurfuryl alcohol resin which is carbonized and fired to form the integral vitreous carbon body and the device is activated by neutron bombardment of the thulium-169 to produce the beta-emitting thulium-170

  7. Tissue reactions in lambs and kids vaccinated with irradiated and normal amphistome metacercariae (Cercariae indicae XXVI)

    International Nuclear Information System (INIS)

    Hafeez, Md.; Rao, B.V.

    1986-01-01

    The intensity of gross and histopathological changes were inversely related to the dose of irradiation. Severe catarrhal enteritis was noticed with non-irradiated metacercariae while with increased irradiation doses the intensity of changes were in decreasing order, however, with 3 Krad dose no severe change was seen. The severe changes of gastro-enteritic lesions were seen from the challenge dose of normal metacercariae in the lambs and kids previously vaccinated with non-irradiated metacercariae. The moderate catarrhal enteritis, mild necrotic lesions and absence of severe lesions produced by the challenge dose of normal metacercariae in the lambs and kids previously vaccinated with 2, 2.5 and 3 Krad level of irradiated metacercariae suggested that the lesions produced by challenge doses were in order of reduced intensity as the dose of irradiation for initial vaccination increased. The cellular infiltration with round cells, plasma cells and macrophages in the mucosa of the small intestine was more in lambs and kids vaccinated with irradiated metacercariae and the order of increase was in correspondent with the level of irradiation. The present study showed that the optimal dose of irradiation for amphistome metacercariae was 3 Krad, where maximum immunological response could be obtained. This also suggests the possibility of immunizing lambs and kids against intestinal amphistomiasis with 3 Krad irradiated metacercariae. (author)

  8. Histopathological investigation of radiation necrosis. Coagulation necrosis in the irradiated and non-irradiated brain tumors and in the normal brain tissue

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    Nakamura, N [Niigata Univ. (Japan). Brain Research Inst.

    1977-01-01

    Eighty four irradiated tumors (including 59 gliomas) and the surrounding brain tissue were analyzed. In 'normal' brain tissue, typical coagulation necrosis attributable to irradiation was observed in the cerebral white matter, presenting a whitish-yellow color but no remarkable changes in volume. Histologically there was complete desintegration of myelin and axon. Vascular changes included hyalinous thickening, concentric cleavage, fibrinoid degeneration, adventitial fibrosis and edema of small arteries, fibrin thrombi or occlusion of arterioles and capillaries, and telangiectasia of small veins and venules. While other tumors showed hyalinous or fibrous scar tissue and decrease in volume, the gliomas maintained their original volume without residual tumor cells. Massive coagulation necrosis was occasionally found even in full volume, non-irradiated gliomas (controls), although the changes were fewer and not so varied as in typical radiation necrosis. With small dosages, it was difficult to judge whether the necrosis was caused by irradiation or occurred spontaneously. Coagulation necrosis in tumor tissue was found in 25 of 59 cases (42%) of irradiated gliomas, but in only 2 of 49 cases (4%) of the nonirradiated gliomas. In 49 cases no coagulation necrosis of the surrounding tissue was found. Although histopathological judgement is difficult, it is suggested that there is a significant correlation between coagulation necrosis and irradiation. Discussion of the relationship between coagulation necrosis and NSD (nominal standard dose) led to the conclusion that coagulation necrosis will not be caused by irradiation of less than 1400 rets in NSD.

  9. Changes in regional blood flow of normal and tumor tissues following hyperthermia and combined X-ray irradiation

    International Nuclear Information System (INIS)

    Suga, Kazuyoshi

    1986-01-01

    Hyperthermia and X-ray irradiation were given to Ehrlich tumors, which were induced in the ventrum of the right hind foot of ICR mice, and to the normal tissues. Their effects on regional blood flow were examined using Xe-133 local clearance method. Blood flow of the normal tissues remained unchanged by heating at 41 deg C for 30 minutes, and increased by heating at 43 deg C and 45 deg C for 30 minutes. On the contrary, blood flow of the tumors decreased with an increase in temperature. When hypertermia (43 deg C for 30 minutes) was combined with irradiation of 30 Gy, decrease in blood flow of the tumors was greater than the normal tissues at 24 hours. Blood flow of the tumors depended on tumor size. The decreased amount of blood flow by hyperthermia was more for tumors > 250 mm 3 than tumors 3 . Blood flow ratios of tumor to normal tissues were also smaller in tumors > 250 mm 3 than tumors 3 . In the case of tumors 3 , blood flow tended to return to normal at 3 hr after heating at 43 deg C for 30 min. However, this was not seen in tumors > 250 mm 3 . (Namekawa, K.)

  10. Iso-effect tables for tolerance of irradiated normal human tissues

    International Nuclear Information System (INIS)

    Cohen, L.; Creditor, M.

    1983-01-01

    Available literature on a radiation injury to human tissues (lung, brain, kidney and intestine) was surveyed. A parameter search program (RAD3) was used to derive best-fitting cell kinetic parameters, on the assumption that radiation injury arises from depletion of parenchymal cells in the irradiated organs. From these parameters iso-effect tables were constructed for a wide range of treatment schedules, including daily treatment as well as fractionation at longer intervals, for each tissue. The tables provide a set of limiting doses, above which the risk of radiation injury becomes substantial. Tolerance limits and dose-time-factors were substantially different in the four tissues. It is concluded that computed iso-effect tables provide a more reliable guide to treatment than conventional time-dose equations

  11. Neutron RBE for normal tissues

    International Nuclear Information System (INIS)

    Field, S.B.; Hornsey, S.

    1979-01-01

    RBE for various normal tissues is considered as a function of neutron dose per fraction. Results from a variety of centres are reviewed. It is shown that RBE is dependent on neutron energy and is tissue dependent, but is not specially high for the more critical tissues or for damage occurring late after irradiation. (author)

  12. SU-F-T-150: Comparing Normal Tissue Irradiated Volumes for Proton Vs. Photon Treatment Plans On Lung Patients

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    Liu, A; Mohan, R; Liao, Z [UT MD Anderson Cancer Center, Houston, TX (United States)

    2016-06-15

    Purpose: The aim of this work is to compare the “irradiated volume” (IRV) of normal tissues receiving 5, 20, 50, 80 and 90% or higher of the prescription dose with passively scattered proton therapy (PSPT) vs. IMRT of lung cancer patients. The overall goal of this research is to understand the factors affecting outcomes of a randomized PSPT vs. IMRT lung trial. Methods: Thirteen lung cancer patients, selected randomly, were analyzed. Each patient had PSPT and IMRT 74 Gy (RBE) plans meeting the same normal tissue constraints generated. IRVs were created for pairs of IMRT and PSPT plans on each patient. The volume of iGTV, (respiratory motion-incorporated GTV) was subtracted from each IRV to create normal tissue irradiated volume IRVNT. The average of IRVNT DVHs over all patients was also calculated for both modalities and inter-compared as were the selected dose-volume indices. Probability (p value) curves were calculated based on the Wilcoxon matched-paired signed-rank test to determine the dose regions where the statistically significant differences existed. Results: As expected, the average 5, 20 and 50% IRVNT’s for PSPT was found to be significantly smaller than for IMRT (p < 0.001, 0.01, and 0.001 respectively). However, the average 90% IRVNT for PSPT was greater than for IMRT (p = 0.003) presumably due to larger penumbra of protons and the long range of protons in lower density media. The 80% IRVNT for PSPT was also larger but not statistically distinguishable (p = .224). Conclusion: PSPT modality has smaller irradiated volume at lower doses, but larger volume at high doses. A larger cohort of lung patients will be analyzed in the future and IRVNT of patients treated with PSPT and IMRT will be compared to determine if the irradiated volumes (the magnitude of “dose bath”) correlate with outcomes.

  13. Impairments of DNA synthesization and normal tissue after irradiation with carbon ions

    International Nuclear Information System (INIS)

    Takai, Nobuhiko; Watanabe, Masahiko; Ando, Koichi; Furusawa, Yoshiya; Uzawa, Akiko; Koike, Sachiko; Fukawa, Takeshi; Monobe, Manami; Hirayama, Ryoichi

    2006-01-01

    The purpose of this study is to evaluate [2- 14 C]thymidine as a tracer, to detect radiation damages in gut. We examined the radiolabeled thymidine accumulation in gut after irradiated with carbon-ion. Mice were given whole body irradiation with carbon-ion (290 MeV/u, 6 cm-spread-out Bragg peak (SOBP), 20 keV/μm). Gut [2- 14 C]thymidine accumulation significantly decreased 4 hr after irradiated with 9 Gy, and did not recover until 24 hr after irradiation. Furthermore, we investigated the dose dependency of [2- 14 C]thymidine accumulation in gut. At 12 hr after irradiation, accumulation of thymidine decreased with an increase of carbon-ion doses (1-9 Gy), whereas that of [6- 3 H]thymidine was independent of radiation dose. These results suggest that the difference of isotope-labeled position causes change of thymidine kinetics. At 84 hr after irradiation, [2- 14 C]thymidine accumulation showed no dose dependence. However, a clear dose dependence was obtained when [2- 14 C]thymidine accumulation was corrected by blood flow. Uptake of a regional blood flow marker 14 C-N-isopropyl-p-iodoamphetamine (IMP) in gut increased after 9-18 Gy irradiation. These findings demonstrated that the [2- 14 C]thymidine uptake in vivo could be an appropriate marker for investigating gut responses and blood flow should be taken account for the evaluation by [2- 14 C]thymidine. (author)

  14. Investigation of normal tissue complication probabilities in prostate and partial breast irradiation radiotherapy techniques

    International Nuclear Information System (INIS)

    Bezak, E.; Takam, R.; Bensaleh, S.; Yeoh, E.; Marcu, L.

    2011-01-01

    Full text: Normal- Tissue-Complication Probabilities of rectum, bladder and urethra following various radiation techniques for prostate cancer were evaluated using the relative-seriality and Lyman models. NTCPs of lungs, heart and skin, their dependence on sourceposition, balloon-deformation were also investigated for HDR mammosite brachytherapy. The prostate treatment techniques included external three dimentional conformal-radiotherapy, Low-Dose-Rate brachytherapy (1-125), High-Dose-Rate brachytherapy (Ir-I92). Dose- Volume-Histograms of critical structures for prostate and breast radiotherapy, retrieved from corresponding treatment planning systems, were converted to Biological Effective Dose (BEffD)-based and Equivalent Dose(Deq)-based DVHs to account for differences in radiation delivery and fractionation schedule. Literature-based model parameters were used to calculate NTCPs. Hypofractionated 3D-CRT (2.75 Gy/fraction, total dose 55 Gy) NTCPs of rectum, bladder and urethra were less than those for standard fractionated 4-field 3D-CRT (2-Gy/fraction, 64 Gy) and dose-escalated 4- and 5-field 3D-CRT (74 Gy). Rectal and bladder NTCPs (5.2% and 6.6%) following the dose-escalated 4-field 3D-CRT (74 Gy) were the highest among analyzed techniques. The average NTCP for rectum and urethra were 0.6% and 24.7% for LDRBT and 0.5% and 11.2% for HDR-BT. For Mammosite, NTCP was estimated to be 0.1 %, 0.1 %, 1.2% and 3.5% for skin desquamation, erythema, telangiectasia and fibrosis respectively (the source positioned at the balloon centre). A 4 mm Mammosite-balloon deformation leads to overdosing of PTV regions by ∼40%, resulting in excessive skin dose and increased NTCP. Conclusions Prostate brachytherapy resulted in NTCPs lower compared to external beam techniques. Mammosite-brachytherapy resulted in no heart/lung complications regardless of balloon deformation. However, 4 mm deformation caused 0.6% increase in tissue fibrosis NTCP.

  15. Changes in the rate of proliferation in normal tissues after irradiation

    International Nuclear Information System (INIS)

    Denekamp, J.

    1975-01-01

    In tissues where reproductive cell death is known to cause the functional tissue damage (e.g., intestine and skin), repopulation becomes important only after the death of the radiation-damaged cells. Since these tissues have a fairly rapid turnover, this can occur within a short period of time and can assist in the healing of tissues during fractionated therapy. However, in tissues which express their damage late, such as the lung, it is very unlikely that repopulation will be stimulated before cell death is manifested and this does not occur during the period over which fractionated radiotherapy is administered. Although repopulation may be of no importance in these tissues, e.g., lungs and kidneys, there appears to be some other ''repair'' process which requires additional radiation dose to be administered to achieve the same endpoint if the overall time is increased

  16. Estimating functional liver reserve following hepatic irradiation: Adaptive normal tissue response models

    International Nuclear Information System (INIS)

    Stenmark, Matthew H.; Cao, Yue; Wang, Hesheng; Jackson, Andrew; Ben-Josef, Edgar; Ten Haken, Randall K.; Lawrence, Theodore S.; Feng, Mary

    2014-01-01

    Purpose: To estimate the limit of functional liver reserve for safe application of hepatic irradiation using changes in indocyanine green, an established assay of liver function. Materials and methods: From 2005 to 2011, 60 patients undergoing hepatic irradiation were enrolled in a prospective study assessing the plasma retention fraction of indocyanine green at 15-min (ICG-R15) prior to, during (at 60% of planned dose), and after radiotherapy (RT). The limit of functional liver reserve was estimated from the damage fraction of functional liver (DFL) post-RT [1 − (ICG-R15 pre-RT /ICG-R15 post-RT )] where no toxicity was observed using a beta distribution function. Results: Of 48 evaluable patients, 3 (6%) developed RILD, all within 2.5 months of completing RT. The mean ICG-R15 for non-RILD patients pre-RT, during-RT and 1-month post-RT was 20.3%(SE 2.6), 22.0%(3.0), and 27.5%(2.8), and for RILD patients was 6.3%(4.3), 10.8%(2.7), and 47.6%(8.8). RILD was observed at post-RT damage fractions of ⩾78%. Both DFL assessed by during-RT ICG and MLD predicted for DFL post-RT (p < 0.0001). Limiting the post-RT DFL to 50%, predicted a 99% probability of a true complication rate <15%. Conclusion: The DFL as assessed by changes in ICG during treatment serves as an early indicator of a patient’s tolerance to hepatic irradiation

  17. Radiotherapy. Non-standard fractionated regimens improving cancer treatment. Part II. Response of normal tissues to fractionated irradiation

    International Nuclear Information System (INIS)

    Villar, A.; Hernandez, M.; Pera, J.; Cambray, M.; Villa, S.; Arnaiz, M.D.

    1988-01-01

    The phenomena participating in the response of tissues to fractionated irradiation are analyzed with special emphasis on the most relevant points influencing the design of non-standard fractionated regimens. (Author)

  18. Radiorestoring activity of few nucleotides on normal tissues of Jerusalem Artichoke after an irradiation with γ rays of 60Co

    International Nuclear Information System (INIS)

    Jonard, Robert; Bayonove, Jacqueline; Riedel, Michel.

    1978-01-01

    The nucleotides tested: adenosine triphosphate (ATP) and cyclic adenosine 3',5'-monophosphate (3',5'-cAMP), guanosine triphosphate (GTP) and cyclic guanosine 3',5'-monophosphate (3',5'-cGMP), are able to restore proliferation to irradiatedirradiation, 3,000 rad) Jesusalem Artichoke tissue. The 3',5'-cGMP shows the greater radiorestoring activity [fr

  19. Comparison of single, fractionated and hyperfractionated irradiation on the development of normal tissue damage in rat lung

    International Nuclear Information System (INIS)

    Giri, P.G.S.; Kimler, B.F.; Giri, U.P.; Cox, G.G.; Reddy, E.K.

    1985-01-01

    The effect of fractionated thoracic irradiation on the development of normal tissue damage in rats was compared to that produced by single doses. Animals received a single dose of 15 Gy, 30 Gy in 10 daily fractions of 3 Gy each (fractionation), or 30 Gy in 30 fractions of 1 Gy each 3 times a day (hyperfractionation). The treatments produced minimal lethality since a total of only 6 animals died between days 273 and 475 after the initiation of treatment, with no difference in survival observed between the control and any of the 3 treated groups. Despite the lack of lethality, evidence of lung damage was obtained by histological examination. Animals that had received either single doses or fractionated doses had more of the pulmonary parenchyma involved than did animals that had received hyperfractionated doses. The authors conclude that, in the rat lung model, a total radiation dose of 30 Gy fractionated over 14 days produces no more lethality nor damage to lung tissue than does 15 Gy delivered as a single dose. However, long-term effects as evidenced by deposits of collagen and development of fibrosis are significantly reduced by hyperfractionation when compared to single doses and daily fractionation

  20. Suberoylanilide hydroxamic acid affects γH2AX expression in osteosarcoma, atypical teratoid rhabdoid tumor and normal tissue cell lines after irradiation

    International Nuclear Information System (INIS)

    Blattmann, C.; Oertel, S.; Thiemann, M.; Weber, K.J.; Schmezer, P.; Zelezny, O.; Lopez Perez, R.; Kulozik, A.E.; Debus, J.; Ehemann, V.

    2012-01-01

    Osteosarcoma and atypical teratoid rhabdoid tumors are tumor entities with varying response to common standard therapy protocols. Histone acetylation affects chromatin structure and gene expression which are considered to influence radiation sensitivity. The aim of this study was to investigate the effect of the combination therapy with the histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA) and irradiation on atypical teratoid rhabdoid tumors and osteosarcoma compared to normal tissue cell lines. Clonogenic assay was used to determine cell survival. DNA double-strand breaks (DSB) were examined by pulsed-field electrophoresis (PFGE) as well as by γH2AX immunostaining involving flow cytometry, fluorescence microscopy, and immunoblot analysis. SAHA lead to an increased radiosensitivity in tumor but not in normal tissue cell lines. γH2AX expression as an indicator for DSB was significantly increased when SAHA was applied 24 h before irradiation to the sarcoma cell cultures. In contrast, γH2AX expression in the normal tissue cell lines was significantly reduced when irradiation was combined with SAHA. Analysis of initial DNA fragmentation and fragment rejoining by PFGE, however, did not reveal differences in response to the SAHA pretreatment for either cell type. SAHA increases radiosensitivity in tumor but not normal tissue cell lines. The increased H2AX phosphorylation status of the SAHA-treated tumor cells post irradiation likely reflects its delayed dephosphorylation within the DNA damage signal decay rather than chromatin acetylation-dependent differences in the overall efficacy of DSB induction and rejoining. The results support the hypothesis that combining SAHA with irradiation may provide a promising strategy in the treatment of solid tumors. (orig.)

  1. The use of biological isodoses ''IsobioGy 2'' for evaluation of tumour and normal tissues response for fractionated irradiation

    International Nuclear Information System (INIS)

    Maciejewski, B.; Skolyszewski, J.; Majewski, S.; Lobodziec, W.; Jedynak, T.; Slosarek, K.

    1988-01-01

    Divergences between physical and biological dose distributions were analysed using linear quadratic model. It was found that small variations in physical dose distribution and differences in normal tissue sensitivity for change in dose per fraction, expressed by a α/β value, can cause a high difference between physical and biological doses. This difference significantly increases when one field instead of two fields is daily treated. If there is no enough separation between treated fields, the biological dose may dramatically increase. The use of biological ''isobioGy 2'' isodoses, instead of physical isodoses, can provide an important information on biological effect in tumour or normal tissue and may diminish the risk of giving too high dose to normal tissue and too low dose to the tumour. 6 figs., 13 refs. (author)

  2. SU-E-T-501: Normal Tissue Toxicities of Pulsed Low Dose Rate Radiotherapy and Conventional Radiotherapy: An in Vivo Total Body Irradiation Study

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    Cvetkovic, D; Zhang, P; Wang, B; Chen, L; Ma, C [Fox Chase Cancer Center, Philadelphia, PA (United States)

    2014-06-01

    Purpose: Pulsed low dose rate radiotherapy (PLDR) is a re-irradiation technique for therapy of recurrent cancers. We have previously shown a significant difference in the weight and survival time between the mice treated with conventional radiotherapy (CRT) and PLDR using total body irradiation (TBI). The purpose of this study was to investigate the in vivo effects of PLDR on normal mouse tissues.Materials and Methods: Twenty two male BALB/c nude mice, 4 months of age, were randomly assigned into a PLDR group (n=10), a CRT group (n=10), and a non-irradiated control group (n=2). The Siemens Artiste accelerator with 6 MV photon beams was used. The mice received a total of 18Gy in 3 fractions with a 20day interval. The CRT group received the 6Gy dose continuously at a dose rate of 300 MU/min. The PLDR group was irradiated with 0.2Gyx20 pulses with a 3min interval between the pulses. The mice were weighed thrice weekly and sacrificed 2 weeks after the last treatment. Brain, heart, lung, liver, spleen, gastrointestinal, urinary and reproductive organs, and sternal bone marrow were removed, formalin-fixed, paraffin-embedded and stained with H and E. Morphological changes were observed under a microscope. Results: Histopathological examination revealed atrophy in several irradiated organs. The degree of atrophy was mild to moderate in the PLDR group, but severe in the CRT group. The most pronounced morphological abnormalities were in the immune and hematopoietic systems, namely spleen and bone marrow. Brain hemorrhage was seen in the CRT group, but not in the PLDR group. Conclusions: Our results showed that PLDR induced less toxicity in the normal mouse tissues than conventional radiotherapy for the same dose and regimen. Considering that PLDR produces equivalent tumor control as conventional radiotherapy, it would be a good modality for treatment of recurrent cancers.

  3. Normal tissue consequences

    International Nuclear Information System (INIS)

    Anon.

    1989-01-01

    This chapter discusses radiotherapy planning and irradiation effects on the following: pelvis (bone, bone marrow, muscles, genital organs, urinary bladder, urethra, ureter, small intestine, rectum, anus); abdomen (stomach, liver, small intestine, kidneys, adrenal glands, pancreas, spleen); thorax (respiratory system, esophagus, heart, ribs, breasts, brachial plexus, spinal cord); head and neck (salivary glands, teeth, mandible, mucosa, ears, eyes, facial muscles, larynx, thyroid gland, pituitary gland, brain, spinal cord); central nervous system (brain, optic nerves, pituitary gland, scalp, skull, spinal cord); and the extremities

  4. Normal tissue tolerance to external beam radiation therapy: Ovaries; Tolerance a l'irradiation des tissus sains: les ovaires

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    Gross, E.; Champetier, C.; Zaccariotto, A.; Duberge, T.; Guerder, C. [Departement de radiotherapie, hopital de la Timone, 13 - Marseille (France); Pointreau, Y. [Service Corad, pole Henry-S.-Kaplan, CHU Bretonneau, 37 - Tours (France); Ortholan, C. [Service de radiotherapie, centre Antoine-Lacassagne, 06 - Nice (France); Chauvet, B. [Institut Sainte-Catherine, 84 - Avignon (France)

    2010-07-15

    Clinical situations requiring protections of ovaries are mainly paediatric irradiations and pre-menopausal pelvic irradiations. The main complication of ovarian irradiation is the induced castration. Ovaries are extremely radiosensitive organs with strong interpersonal variations. The castrative effect of irradiation depends mainly on two factors: patient's age and the dose delivered to ovaries. The surgical technique of ovarian transposition allows to minimize the dose received by ovaries by taking them away, out of irradiation fields; the aim is to exclude them from the volume receiving 5 Gy or more, and if possible from those receiving 2 Gy. This technique becomes integrated into a multidisciplinary approach of conservation of fertility for patients exposed to other cytotoxic treatments. (authors)

  5. The SOD Mimic, MnTE-2-PyP, Protects from Chronic Fibrosis and Inflammation in Irradiated Normal Pelvic Tissues

    Directory of Open Access Journals (Sweden)

    Shashank Shrishrimal

    2017-11-01

    Full Text Available Pelvic radiation for cancer therapy can damage a variety of normal tissues. In this study, we demonstrate that radiation causes acute changes to pelvic fibroblasts such as the transformation to myofibroblasts and the induction of senescence, which persist months after radiation. The addition of the manganese porphyrin, MnTE-2-PyP, resulted in protection of these acute changes in fibroblasts and this protection persisted months following radiation exposure. Specifically, at two months post-radiation, MnTE-2-PyP inhibited the number of α-smooth muscle actin positive fibroblasts induced by radiation and at six months post-radiation, MnTE-2-PyP significantly reduced collagen deposition (fibrosis in the skin and bladder tissues of irradiated mice. Radiation also resulted in changes to T cells. At two months post-radiation, there was a reduction of Th1-producing splenocytes, which resulted in reduced Th1:Th2 ratios. MnTE-2-PyP maintained Th1:Th2 ratios similar to unirradiated mice. At six months post-radiation, increased T cells were observed in the adipose tissues. MnTE-2-PyP treatment inhibited this increase. Thus, MnTE-2-PyP treatment maintains normal fibroblast function and T cell immunity months after radiation exposure. We believe that one of the reasons MnTE-2-PyP is a potent radioprotector is due to its protection of multiple cell types from radiation damage.

  6. Effect of time intervals between irradiation and chemotherapeutic agents on the normal tissue damage. Comparison between in vivo and in vitro experiments

    Energy Technology Data Exchange (ETDEWEB)

    Ito, Hisao; Nakayama, Toshitake; Hashimoto, Shozo (Keio Univ., Tokyo (Japan). School of Medicine)

    1989-05-01

    Experiments have been carried out to determine the effect on the cell survivals at different time intervals between irradiation and chemotherapeutic agents (BLM, cisDDP, ADM and ACNU) in either the in vivo or the in vitro system. The intestinal epithelial assay was applied on the in vivo system. The clonogenic cell survivals of V/sub 79/ cells, both in the proliferative and the plateau phases, were determined in the in vitro system. The V/sub 79/ cells in the plateau phase were more sensitive to BLM, cisDDP and ACNU than those in the proliferative phase, however, the result was reverse with ADM. When BLM, cisDDP or ACNU was combined with irradiation at different time intervals, the response of the plateau phase V/sub 79/ cells to combination therapies were very similar to those of the intestinal epithelial cells. On the other hand, V/sub 79/ cells in the proliferative phase, which were treated with ADM and irradiation, showed the similar response as the intestinal cells. These results suggest that studies of chemo-radiotherapy with cultured cells which are sensitive to chemotherapeutic agents might be suitable to expect the in vivo damage of the normal tissue. (author).

  7. Comparison of normal tissue dose with three-dimensional conformal techniques for breast cancer irradiation including the internal mammary nodes

    NARCIS (Netherlands)

    van der Laan, Hans Paul; Dolsma, Willemtje; van t Veld, Aart; Bijl, HP; Langendijk, JA

    2005-01-01

    PURPOSE: To compare the Para Mixed technique for irradiation of the internal mammary nodes (IMN) with three commonly used strategies, by analyzing the dose to the heart and other organs at risk. METHODS AND MATERIALS: Four different three-dimensional conformal dose plans were created for 30 breast

  8. HDR monotherapy for prostate cancer: A simulation study to determine the effect of catheter displacement on target coverage and normal tissue irradiation

    International Nuclear Information System (INIS)

    Kolkman-Deurloo, Inger-Karine K.; Roos, Martin A.; Aluwini, Shafak

    2011-01-01

    Purpose: The aim of this study was to systematically analyse the effect of catheter displacements both on target coverage and normal tissue irradiation in fractionated high dose rate (HDR) prostate brachytherapy, using a simulation study, and to define tolerances for catheter displacement ensuring that both target coverage and normal tissue doses remain clinically acceptable. Besides the effect of total implant displacement, also displacements of catheters belonging to selected template rows only were evaluated in terms of target coverage and normal tissue dose, in order to analyse the change in dose distribution as a function of catheter dwell weight and catheter location. Material and methods: Five representative implant geometries, with 17 catheters each, were selected. The clinical treatment plan was compared to treatment plans in which an entire implant displacement in caudal direction over 3, 5, 7 and 10 mm was simulated. Besides, treatment plans were simulated considering a displacement of either the central, most ventral or most dorsal catheter rows only, over 5 mm caudally. Results: Due to displacement of the entire implant the target coverage drops below the tolerance of 93% for all displacements studied. The effect of displacement of the entire implant on organs at risk strongly depended on the patient anatomy; e.g., for 80% of the implant geometries the V 80 of the rectum exceeded its tolerance for all displacements. The effect of displacement of catheters belonging to selected template rows depended strongly on the relative weight of each catheter row when considering the target coverage and on its location when considering the dose in the organs at risk. Conclusion: This study supports the need for a check of the catheter locations before each fraction and correction of deviations of the catheter position exceeding 3 mm.

  9. Modulation of the Rho/ROCK pathway in heart and lung after thorax irradiation reveals targets to improve normal tissue toxicity.

    Science.gov (United States)

    Monceau, Virginie; Pasinetti, Nadia; Schupp, Charlotte; Pouzoulet, Fred; Opolon, Paule; Vozenin, Marie-Catherine

    2010-11-01

    The medical options available to prevent or treat radiation-induced injury are scarce and developing effective countermeasures is still an open research field. In addition, more than half of cancer patients are treated with radiation therapy, which displays a high antitumor efficacy but can cause, albeit rarely, disabling long-term toxicities including radiation fibrosis. Progress has been made in the definition of molecular pathways associated with normal tissue toxicity that suggest potentially effective therapeutic targets. Targeting the Rho/ROCK pathway seems a promising anti-fibrotic approach, at least in the gut; the current study was performed to assess whether this target was relevant to the prevention and/or treatment of injury to the main thoracic organs, namely heart and lungs. First, we showed activation of two important fibrogenic pathways (Smad and Rho/ROCK) in response to radiation-exposure to adult cardiomyocytes; we extended these observations in vivo to the heart and lungs of mice, 15 and 30 weeks post-irradiation. We correlated this fibrogenic molecular imprint with alteration of heart physiology and long-term remodelling of pulmonary and cardiac histological structures. Lastly, cardiac and pulmonary radiation injury and bleomycin-induced pulmonary fibrosis were successfully modulated using Rho/ROCK inhibitors (statins and Y-27632) and this was associated with a normalization of fibrogenic markers. In conclusion, the present paper shows for the first time, activation of Rho/ROCK and Smad pathways in pulmonary and cardiac radiation-induced delayed injury. Our findings thereby reveal a safe and efficient therapeutic opportunity for the abrogation of late thoracic radiation injury, potentially usable either before or after radiation exposure; this approach is especially attractive in (1) the radiation oncology setting, as it does not interfere with prior anti-cancer treatment and in (2) radioprotection, as applicable to the treatment of established

  10. Modulation of the ρ/rock pathway in heart and lung after thorax irradiation reveals targets to improve normal tissue toxicity

    International Nuclear Information System (INIS)

    Monceau, V.; Pasinetti, N.; Schupp, C.; Pouzoulet, F.; Opolon, P.; Vozenin, M.C.

    2010-01-01

    The medical options available to prevent or treat radiation-induced injury are scarce and developing effective countermeasures is still an open research field. In addition, more than half of cancer patients are treated with radiation therapy, which displays a high antitumor efficacy but can cause, albeit rarely, disabling long-term toxicities including radiation fibrosis. Progress has been made in the definition of molecular pathways associated with normal tissue toxicity that suggest potentially effective therapeutic targets. Targeting the Rho/ROCK pathway seems a promising anti-fibrotic approach, at least in the gut; the current study was performed to assess whether this target was relevant to the prevention and/or treatment of injury to the main thoracic organs, namely heart and lungs. First, we showed activation of two important fibro-genic pathways (Smad and Rho/ROCK) in response to radiation-exposure to adult cardio-myocytes; we extended these observations in vivo to the heart and lungs of mice, 15 and 30 weeks post-irradiation. We correlated this fibro-genic molecular imprint with alteration of heart physiology and long-term remodelling of pulmonary and cardiac histological structures. Lastly, cardiac and pulmonary radiation injury and bleomycin-induced pulmonary fibrosis were successfully modulated using Rho/ROCK inhibitors (statins and Y-27632) and this was associated with a normalization of fibro-genic markers. In conclusion, the present paper shows for the first time, activation of Rho/ROCK and Smad pathways in pulmonary and cardiac radiation-induced delayed injury. Our findings thereby reveal a safe and efficient therapeutic opportunity for the abrogation of late thoracic radiation injury, potentially usable either before or after radiation exposure; this approach is especially attractive in (1) the radiation oncology setting, as it does not interfere with prior anti-cancer treatment and in (2) radioprotection, as applicable to the treatment of

  11. Normal tissue tolerance to external beam radiation therapy: Peripheral nerves; Dose de tolerance a l'irradiation des tissus sains: les nerfs peripheriques

    Energy Technology Data Exchange (ETDEWEB)

    Henriques de Figueiredo, B.; Dejean, C.; Sargos, P.; Kantor, G. [Departement de radiotherapie, institut Bergonie, centre regional de lutte contre le cancer, 33 - Bordeaux (France); Huchet, A.; Mamou, N. [Service d' oncologie medicale et de radiotherapie, CHU Saint-Andre, 33 - Bordeaux (France); Loiseau, H. [Service de neurochirurgie, CHU Pellegrin, 33 - Bordeaux (France)

    2010-07-15

    Plexopathies and peripheral neuropathies appear progressively and with several years delay after radiotherapy. These lesions are observed principally after three clinical situations: supraclavicular and axillar irradiations for breast cancer, pelvic irradiations for various pathologies and limb irradiations for soft tissue sarcomas. Peripheral nerves and plexus (brachial and lumbosacral) are described as serial structures and are supposed to receive less than a given maximum dose linked to the occurrence of late injury. Literature data, mostly ancient, define the maximum tolerable dose to a threshold of 60 Gy and highlight also a great influence of fractionation and high fraction doses. For peripheral nerves, most frequent late effects are pain with significant differences of occurrence between 50 and 60 Gy. At last, associated pathologies (diabetes, vascular pathology, neuropathy) and associated treatments have probably to be taken into account as additional factors, which may increase the risk of these late radiation complications. (authors)

  12. Differential superiority of heavy charged-particle irradiation to x-rays: Studies on biological effectivenes and side effect mechanisms in multicellular tumor and normal tissue models

    Directory of Open Access Journals (Sweden)

    Stefan eWalenta

    2016-02-01

    Full Text Available This review is focused on the radiobiology of carbon ions compared to x-rays using multicellular models of tumors and normal mucosa. The first part summarizes basic radiobiological effects, as observed in cancer cells. The second, more clinically oriented part of the review deals with radiation-induced cell migration and mucositis.Multicellular spheroids (MCS from V79 hamster cells were irradiated with x-rays or carbon ions under ambient or restricted oxygen supply conditions. Oxygen enhancement ratios (OER were 2.9, 2.8, and 1.4 for irradiation with photons, 12C+6 in the plateau region, and 12C+6 in the Bragg peak, respectively. A relative biological effectiveness (RBE of 4.3 and 2.1 for ambient pO2 and hypoxia was obtained, respectively. The high effectiveness of carbon ions was reflected by an enhanced accumulation of cells in G2/M, and a dose-dependent massive induction of apoptosis. Clinically relevant doses (3 Gy of x-rays induced an increase in migratory activity of U87 but not of LN229 or HCT116 tumor cells. Such an increase in cell motility following irradiation in situ could be the source of recurrence. In contrast, carbon ion treatment was associated with a dose-dependent decrease in migration with all cell lines and under all conditions investigated. The radiation-induced loss of cell motility was correlated, in most cases, with corresponding changes in 1 integrin expression. Unlike with particles, the photon-induced increase in cell migration was paralleled by an elevated phosphorylation status of the epidermal growth factor receptor (EGFR and AKT-ERK1/2 pathway. Comparing the gene toxicity of x-rays with that of particles using the gamma-H2AX technique in organotypic cultures of the oral mucosa, the superior effectiveness of heavy ions was confirmed by a two-fold higher number of foci per nucleus. Pro-inflammatory signs, however, were similar for both treatment modalities, e. g., the activation of NFkappaB, and the release of IL

  13. Differential Superiority of Heavy Charged-Particle Irradiation to X-Rays: Studies on Biological Effectiveness and Side Effect Mechanisms in Multicellular Tumor and Normal Tissue Models

    Science.gov (United States)

    Walenta, Stefan; Mueller-Klieser, Wolfgang

    2016-01-01

    This review is focused on the radiobiology of carbon ions compared to X-rays using multicellular models of tumors and normal mucosa. The first part summarizes basic radiobiological effects, as observed in cancer cells. The second, more clinically oriented part of the review, deals with radiation-induced cell migration and mucositis. Multicellular spheroids from V79 hamster cells were irradiated with X-rays or carbon ions under ambient or restricted oxygen supply conditions. Reliable oxygen enhancement ratios could be derived to be 2.9, 2.8, and 1.4 for irradiation with photons, 12C+6 in the plateau region, and 12C+6 in the Bragg peak, respectively. Similarly, a relative biological effectiveness of 4.3 and 2.1 for ambient pO2 and hypoxia was obtained, respectively. The high effectiveness of carbon ions was reflected by an enhanced accumulation of cells in G2/M and a dose-dependent massive induction of apoptosis. These data clearly show that heavy charged particles are more efficient in sterilizing tumor cells than conventional irradiation even under hypoxic conditions. Clinically relevant doses (3 Gy) of X-rays induced an increase in migratory activity of U87 but not of LN229 or HCT116 tumor cells. Such an increase in cell motility following irradiation in situ could be the source of recurrence. In contrast, carbon ion treatment was associated with a dose-dependent decrease in migration with all cell lines and under all conditions investigated. The radiation-induced loss of cell motility was correlated, in most cases, with corresponding changes in β1 integrin expression. The photon-induced increase in cell migration was paralleled by an elevated phosphorylation status of the epidermal growth factor receptor and AKT-ERK1/2 pathway. Such a hyperphosphorylation did not occur during 12C+6 irradiation under all conditions registered. Comparing the gene toxicity of X-rays with that of particles using the γH2AX technique in organotypic cultures of the oral mucosa, the

  14. Differential Superiority of Heavy Charged-Particle Irradiation to X-Rays: Studies on Biological Effectiveness and Side Effect Mechanisms in Multicellular Tumor and Normal Tissue Models.

    Science.gov (United States)

    Walenta, Stefan; Mueller-Klieser, Wolfgang

    2016-01-01

    This review is focused on the radiobiology of carbon ions compared to X-rays using multicellular models of tumors and normal mucosa. The first part summarizes basic radiobiological effects, as observed in cancer cells. The second, more clinically oriented part of the review, deals with radiation-induced cell migration and mucositis. Multicellular spheroids from V79 hamster cells were irradiated with X-rays or carbon ions under ambient or restricted oxygen supply conditions. Reliable oxygen enhancement ratios could be derived to be 2.9, 2.8, and 1.4 for irradiation with photons, (12)C(+6) in the plateau region, and (12)C(+6) in the Bragg peak, respectively. Similarly, a relative biological effectiveness of 4.3 and 2.1 for ambient pO2 and hypoxia was obtained, respectively. The high effectiveness of carbon ions was reflected by an enhanced accumulation of cells in G2/M and a dose-dependent massive induction of apoptosis. These data clearly show that heavy charged particles are more efficient in sterilizing tumor cells than conventional irradiation even under hypoxic conditions. Clinically relevant doses (3 Gy) of X-rays induced an increase in migratory activity of U87 but not of LN229 or HCT116 tumor cells. Such an increase in cell motility following irradiation in situ could be the source of recurrence. In contrast, carbon ion treatment was associated with a dose-dependent decrease in migration with all cell lines and under all conditions investigated. The radiation-induced loss of cell motility was correlated, in most cases, with corresponding changes in β1 integrin expression. The photon-induced increase in cell migration was paralleled by an elevated phosphorylation status of the epidermal growth factor receptor and AKT-ERK1/2 pathway. Such a hyperphosphorylation did not occur during (12)C(+6) irradiation under all conditions registered. Comparing the gene toxicity of X-rays with that of particles using the γH2AX technique in organotypic cultures of the oral

  15. Effect of UV laser irradiation on tissue

    International Nuclear Information System (INIS)

    Nakayama, Takeyoshi; Kubo, Uichi

    1992-01-01

    Laser-tissue interactions have been investigated through Electron Probe Micro Analysis (EPMA), UV-visible optical absorption and Fourier Transform Infrared Spectroscopy (FTIR). Three excimer lasers, ArF, KrF and XeCl, were used to irradiate tissue; cow thighbone and gelatin thin film. Features of UV laser irradiation are described. (author)

  16. DNA-repair, cell killing and normal tissue damage

    International Nuclear Information System (INIS)

    Dahm-Daphi, J.; Dikomey, E.; Brammer, I.

    1998-01-01

    Background: Side effects of radiotherapy in normal tissue is determined by a variety of factors of which cellular and genetic contributions are described here. Material and methods: Review. Results: Normal tissue damage after irradiation is largely due to loss of cellular proliferative capacity. This can be due to mitotic cell death, apoptosis, or terminal differentiation. Dead or differentiated cells release cytokines which additionally modulate the tissue response. DNA damage, in particular non-reparable or misrepaired double-strand breaks are considered the basic lesion leading to G1-arrest and ultimately to cell inactivation. Conclusion: Evidence for genetic bases of normal tissue response, cell killing and DNA-repair capacity is presented. However, a direct link of all 3 endpoints has not yet been proved directly. (orig.) [de

  17. Combination of high-intensity focused ultrasound irradiation and hydroxyapatite nanoparticle injection to injure normal goat liver tissue in vivo without costal bone incision.

    Science.gov (United States)

    Liu, L; Xiao, Z; Xiao, Y; Wang, Z; Li, F; Li, M; Peng, X

    2014-10-20

    The aims of this study were to evaluate the in vivo safety of intravenous nano-hydroxyapatite (nano-HA), to explore how nano-HA might influence the effects of high-intensity focused ultrasound (HIFU) on normal liver tissue, and to investigate whether intravenous nano-HA could enhance HIFU for hepatocellular carcinoma ablation in a goat model. The present study, for the first time, indicated that the delivery of abundant nano-HA into the body over short periods of time could be assembled by the hepatic reticuloendothelial system, subsequently leading to a rapid rise of ultrasound-induced overheating, and ultimately resulting in enlargement of the coagulation necrotic area for ablated hepatocellular carcinoma in goats both in vivo and ex vivo. On the other hand, therapeutic doses of nano-HA were much lower than the lethal dose, and consequently presented transient and mild abnormalities of hepatic enzymes and renal function during the first 24 h after nano-HA injection. These results suggested that the combined application of nano-HA and HIFU is potentially a more effective alternative option compared to surgery for hepatocellular carcinoma local ablation in a safe and feasible manner.

  18. Ultrastructural and cytochemical study of membrane alterations in x-irradiated liver tissue from normal and vitamin E-deficient ducklings

    International Nuclear Information System (INIS)

    Huijbers, W.A.R.; Oosterbaan, J.A.; Meskendorp-Haarsma, T.J.; Hardonk, M.J.; Molenaar, I.

    1979-01-01

    An investigation into the differential susceptibility of liver cellular membranes to peroxidative processes has been performed, using x irradiation on the liver surface, resulting in a a 3-mm penetrating gradient of membrane damage. Ultrastructural, cytochemical, and histochemical findings in this area point to a differential sensitivity of cellular membranes to x irradiation. The plasma membrane and the lysosomal membrane, containing much lipid and cholesterol and little membrane and the lysosomal membrane, containing much lipid and cholesterol and little vitamin E, are highly susceptible to x irradiation. Less sensitive are the membranes of mitochondria and endoplasmic reticulum, containing relatively much vitamin E and proteins and a lower amount of lipids and cholesterol

  19. Mathematical model of normal tissue injury in telegammatherapy

    International Nuclear Information System (INIS)

    Belov, S.A.; Lyass, F.M.; Mamin, R.G.; Minakova, E.I.; Raevskaya, S.A.

    1983-01-01

    A model of normal tissue injury as a result of exposure to ionizing radiation is based on an assumption that the degree of tissue injury is determined by the degree of destruction by certain critical cells. The dependence of the number of lethal injuriies on a single dose is expressed by a trinomial - linear and quadratic parts and a constant, obtained as a result of the processing of experimental data. Quantitative correlations have been obtained for the skin and brain. They have been tested using clinical and experimental material. The results of the testing point out to the absence of time dependence on a single up to 6-week irradiation cources. Correlation with an irradiation field has been obtained for the skin. A conclusion has been made that the concept of isoefficacy of irradiation cources is conditional. Spatial-time fractionation is a promising direction in the development of radiation therapy

  20. Role of endothelium in radiation-induced normal tissue damages

    International Nuclear Information System (INIS)

    Milliat, F.

    2007-05-01

    More than half of cancers are treated with radiation therapy alone or in combination with surgery and/or chemotherapy. The goal of radiation therapy is to deliver enough ionising radiation to destroy cancer cells without exceeding the level that the surrounding healthy cells can tolerate. Unfortunately, radiation-induced normal tissue injury is still a dose limiting factor in the treatment of cancer with radiotherapy. The knowledge of normal tissue radiobiology is needed to determine molecular mechanisms involved in normal tissue pathogenic pathways in order to identify therapeutic targets and develop strategies to prevent and /or reduce side effects of radiation therapy. The endothelium is known to play a critical role in radiation-induced injury. Our work shows that endothelial cells promote vascular smooth muscle cell proliferation, migration and fibro-genic phenotype after irradiation. Moreover, we demonstrate for the first time the importance of PAI-1 in radiation-induced normal tissue damage suggesting that PAI-1 may represent a molecular target to limit injury following radiotherapy. We describe a new role for the TGF-b/Smad pathway in the pathogenesis of radiation-induced damages. TGF-b/Smad pathway is involved in the fibro-genic phenotype of VSMC induced by irradiated EC as well as in the radiation-induced PAI-1 expression in endothelial cells. (author)

  1. Normal tissue tolerance to external beam radiation therapy: Testicles; Dose de tolerance a l'irradiation des tissus sain: les testicules

    Energy Technology Data Exchange (ETDEWEB)

    Champetier, C.; Gross, E.; Zaccariotto, A.; Duberge, T.; Guerder, C. [Service de radiotherapie, hopital de la Timone, 13 - Marseille (France); Pointreau, Y. [Pole Henry-S.-Kaplan, CHU Bretonneau, 37 - Tours (France); Ortholan, C. [Centre Antoine-Lacassagne, 06 - Nice (France); Chauvet, B. [Institut Sainte-Catherine, 84 - Avignon (France)

    2010-07-15

    Although there is very little evidence for direct irradiation of the testes, they may receive significant doses, especially in the treatment of pelvic tumors in adults and in pediatrics. The exocrine function of the testis seems to be more sensitive to radiotherapy. There is a risk of sterility, even after low doses of radiation. In the adult or the child who has reached puberty, we should propose a self-preservation of semen prior to radiotherapy. In pre-pubescent children, the problem is more delicate. In all cases, it is necessary to limit the dose to the testicles without affecting the coverage of tumour volume. Patients and/or their care-givers should be systematically informed of the risk of infertility related to irradiation. (authors)

  2. Radiogenomics: predicting clinical normal tissue radiosensitivity

    DEFF Research Database (Denmark)

    Alsner, Jan

    2006-01-01

    Studies on the genetic basis of normal tissue radiosensitivity, or  'radiogenomics', aims at predicting clinical radiosensitivity and optimize treatment from individual genetic profiles. Several studies have now reported links between variations in certain genes related to the biological response...... to radiation injury and risk of normal tissue morbidity in cancer patients treated with radiotherapy. However, after these initial association studies including few genes, we are still far from being able to predict clinical radiosensitivity on an individual level. Recent data from our own studies on risk...

  3. Extravascular transport in normal and tumor tissues.

    Science.gov (United States)

    Jain, R K; Gerlowski, L E

    1986-01-01

    The transport characteristics of the normal and tumor tissue extravascular space provide the basis for the determination of the optimal dosage and schedule regimes of various pharmacological agents in detection and treatment of cancer. In order for the drug to reach the cellular space where most therapeutic action takes place, several transport steps must first occur: (1) tissue perfusion; (2) permeation across the capillary wall; (3) transport through interstitial space; and (4) transport across the cell membrane. Any of these steps including intracellular events such as metabolism can be the rate-limiting step to uptake of the drug, and these rate-limiting steps may be different in normal and tumor tissues. This review examines these transport limitations, first from an experimental point of view and then from a modeling point of view. Various types of experimental tumor models which have been used in animals to represent human tumors are discussed. Then, mathematical models of extravascular transport are discussed from the prespective of two approaches: compartmental and distributed. Compartmental models lump one or more sections of a tissue or body into a "compartment" to describe the time course of disposition of a substance. These models contain "effective" parameters which represent the entire compartment. Distributed models consider the structural and morphological aspects of the tissue to determine the transport properties of that tissue. These distributed models describe both the temporal and spatial distribution of a substance in tissues. Each of these modeling techniques is described in detail with applications for cancer detection and treatment in mind.

  4. Effects of pions on normal tissues

    International Nuclear Information System (INIS)

    Tokita, N.

    1981-01-01

    Verification of the uniform biological effectiveness of pion beams of various dimensions produced at LAMPF has been made using cultured mammalian cells and mouse jejunum. Normal tissue radiobiology studies at LAMPF are reviewed with regard to biological beam characterization for the therapy program and the current status of acute and late effect studies on rodents

  5. Normal tissue tolerance to external beam radiation therapy: Rectum; Dose de tolerance a l'irradiation des tissus sains: le rectum

    Energy Technology Data Exchange (ETDEWEB)

    Blanchard, P. [Departement de radiotherapie, institut Gustave-Roussy, 94 - Villejuif (France); Chapet, O. [Service d' oncologie-radiotherapie, centre hospitalier Lyon-Sud, 69 - Pierre-Benite (France)

    2010-07-15

    Radiation proctitis is among the most frequent radiation-induced toxicities. This is related to the high frequency of pelvic tumours and the key role of radiotherapy in the treatment of these tumours. Late rectal toxicity usually occurs within the first two years after the completion of a radiotherapy course. Rectal bleeding and a rectal syndrome are the main symptoms, and can be associated to fistulas or rectal ulcers. Clinical factors, such as diabetes mellitus, a severe acute radiation toxicity, small rectal volume or radiation hypersensitivity, are associated with late rectal toxicity. Dosimetric factors derived from the analysis of dose-volume histograms can also predict the occurrence of radiation proctitis, and help to adapt the prescribed dose and the ballistic of irradiation. (authors)

  6. Normal tissue tolerance to external beam radiation therapy: The stomach; Dose de tolerance a l'irradiation des tissus sains: l'estomac

    Energy Technology Data Exchange (ETDEWEB)

    Oberdiac, P. [Service de radiotherapie, hopital de Bellevue, CHU de Saint-Etienne, 42 - Saint-Etienne (France); Mineur, L. [Unite d' oncologie digestive et radiotherapie, institut Sainte-Catherine, 84 - Avignon (France)

    2010-07-15

    In the following article, we will discuss general issues relating to acute and late gastric's radiation toxicities. The tolerance of the stomach to complete or partial organ irradiation is more un-appreciated than for most other organs. We consulted the Medline database via PubMed and used the key words gastric - radiotherapy - toxicity. Currently, 60 Gy or less is prescribed in gastric radiation therapy. Acute clinical toxicity symptoms are predominantly nausea and vomiting. Although there is a general agreement that the whole stomach tolerance is for doses of 40 to 45 Gy without unacceptable complication, it is well established that a stomach dose of 35 Gy increases the risk of ulcer complications. (authors)

  7. Large animal normal tissue tolerance with boron neutron capture.

    Science.gov (United States)

    Gavin, P R; Kraft, S L; DeHaan, C E; Swartz, C D; Griebenow, M L

    1994-03-30

    Normal tissue tolerance of boron neutron capture irradiation using borocaptate sodium (NA2B12H11SH) in an epithermal neutron beam was studied. Large retriever-type dogs were used and the irradiations were performed by single dose, 5 x 10 dorsal portal. Fourteen dogs were irradiated with the epithermal neutron beam alone and 35 dogs were irradiated following intravenous administration of borocaptate sodium. Total body irradiation effect could be seen from the decreased leukocytes and platelets following irradiation. Most values returned to normal within 40 days postirradiation. Severe dermal necrosis occurred in animals given 15 Gy epithermal neutrons alone and in animals irradiated to a total peak physical dose greater than 64 Gy in animals following borocaptate sodium infusion. Lethal brain necrosis was seen in animals receiving between 27 and 39 Gy. Lethal brain necrosis occurred at 22-36 weeks postirradiation. A total peak physical dose of approximately 27 Gy and blood-boron concentrations of 25-50 ppm resulted in abnormal magnetic resonance imaging results in 6 months postexamination. Seven of eight of these animals remained normal and the lesions were not detected at the 12-month postirradiation examination. The bimodal therapy presents a complex challenge in attempting to achieve dose response assays. The resultant total radiation dose is a composite of low and high LET components. The short track length of the boron fission fragments and the geometric effect of the vessels causes much of the intravascular dose to miss the presumed critical target of the endothelial cells. The results indicate a large dose-sparing effect from the boron capture reactions within the blood.

  8. Large animal normal tissue tolerance with boron neutron capture

    International Nuclear Information System (INIS)

    Gavin, P.R.; Swartz, C.D.; Kraft, S.L.; Briebenow, M.L.; DeHaan, C.E.

    1994-01-01

    Normal tissue tolerance of boron neutron capture irradiation using borocaptate sodium (NA 2 B 12 H 11 SH) in an epithermal neutron beam was studied. Large retriever-type dogs were used and the irradiations were performed by single dose, 5 x 10 dorsal portal. Fourteen dogs were irradiated with the epithermal neutron beam alone and 35 dogs were irradiated following intravenous administration of borocaptate sodium. Total body irradiation effect could be seen from the decreased leukocytes and platelets following irradiation. Most values returned to normal within 40 days postirradiation. Severe dermal necrosis occurred in animals given 15 Gy epithermal neutrons alone and in animals irradiated to a total peak physical dose greater than 64 Gy in animals following borocaptate sodium infusion. Lethal brain necrosis was seen in animals receiving between 27 and 39 Gy. Lethal brain necrosis occurred at 22-36 weeks postirradiation. A total peak physical dose of approximately 27 Gy and blood-boron concentrations of 25-50 ppm resulted in abnormal magnetic resonance imaging results in 6 months postexamination. Seven of eight of these animals remained normal and the lesions were not detected at the 12-month postirradiation examination. The bimodal therapy presents a complex challenge in attempting to achieve dose response assays. The resultant total radiation dose is a composite of low and high LET components. The short track length of the boron fission fragments and the geometric effect of the vessels causes much of the intravascular dose to miss the presumed critical target of the endothelial cells. The results indicate a large dose-sparing effect from the boron capture reactions within the blood. 23 refs., 6 figs., 2 tabs

  9. Taurine content of tissues of irradiated rats

    International Nuclear Information System (INIS)

    Akhalaya, M.Ya.; Bogatyrev, G.P.; Kudryashov, Yu.B.; Yartsev, E.I.

    1976-01-01

    The taurine content of tissues (liver, stomach, small intestine and spleen) of rats irradiated with doses of 700 and 450 rads has been studied. Phase changes have been found in the taurine content of radiosensitive tissues in the course of radiation injury development

  10. Normal tissue tolerance to external beam radiation therapy: Spinal cord; Tolerance a l'irradiation des tissus sains: moelle epiniere

    Energy Technology Data Exchange (ETDEWEB)

    Habrand, J.L. [Departement de radiotherapie, institut Gustave-Roussy, 94 - Villejuif (France); Centre de protontherapie, institut Curie, 91 - Orsay (France); Drouet, F. [Departement de radiotherapie, centre Rene-Gauducheau, 44 - Nantes (France)

    2010-07-15

    Radiation myelopathy is one of the most dreadful complications of radiation therapy. Despite multiple animal experiments and human autopsic series, its pathogenesis remains largely unknown. In most instances, the classical aspect of myelomalacia combines glial and vascular injuries in various sequences. Recent studies point out the role of oligo-dendrocytes and their precursors, as well as of intercellular mediators (cytokines and stress molecules). The clinical presentation comprises a spectrum of non specific neurological symptoms whose evolution is sometimes regressive but more commonly progressive and life-threatening. Usually, it occurs following a latent period of six months to two years after irradiation of the cervical, thoracic or upper lumbar spine to a dose in excess of 50 Gy, conventionally fractionated. Nonetheless, these typical features can be altered by extrinsic factors, such as hypo fractionation/acceleration of the dose, multiple surgical procedures, chemotherapy especially mega therapy, or neurotoxic drugs. Conversely, hyperfractionated regimens that take into account protracted half-time repair of sublethal damages to the CNS, as well as sophisticated estimates of the dose to the cord and QA programs during the treatment course minimize such risks. (authors)

  11. Normal tissue complication probability (NTCP), the clinician,s perspective

    International Nuclear Information System (INIS)

    Yeoh, E.K.

    2011-01-01

    Full text: 3D radiation treatment planning has enabled dose distributions to be related to the volume of normal tissues irradiated. The dose volume histograms thus derived have been utilized to set NTCP dose constraints to facilitate optimization of treatment planning. However, it is not widely appreciated that a number of important variables other than DYH's which determine NTCP in the individual patient. These variables will be discussed under the headings of patient and treatment related as well as tumour related factors. Patient related factors include age, co-morbidities such as connective tissue disease and diabetes mellitus, previous tissue/organ damage, tissue architectural organization (parallel or serial), regional tissue/organ and individual tissue/organ radiosensitivities as well as the development of severe acute toxicity. Treatment related variables which need to be considered include dose per fraction (if not the conventional 1.8012.00 Gy/fraction, particularly for IMRT), number of fractions and total dose, dose rate (particularly if combined with brachytherapy) and concurrent chemotherapy or other biological dose modifiers. Tumour related factors which impact on NTCP include infiltration of normal tissue/organ usually at presentation leading to compromised function but also with recurrent disease after radiation therapy as well as variable tumour radiosensitivities between and within tumour types. Whilst evaluation of DYH data is a useful guide in the choice of treatment plan, the current state of knowledge requires the clinician to make an educated judgement based on a consideration of the other factors.

  12. Radiobiology in clinical radiation therapy - Part III: Normal tissue damage

    International Nuclear Information System (INIS)

    Travis, Elizabeth L.

    1996-01-01

    Objective: This is the third part of a course designed for residents in radiation oncology preparing for their boards. This part of the course will focus on the mechanisms underlying damage in normal tissues. Although conventional wisdom long held that killing and depletion of a critical cell(s) in a tissue was responsible for the later expression of damage, histopathologic changes in normal tissue can now be explained and better understood in terms of the new molecular biology. The concept that depletion of a single cell type is responsible for the observed histopathologic changes in normal tissues has been replaced by the hypothesis that damage results from the interaction of many different cell systems, including epithelial, endothelial, macrophages and fibroblasts, via the production of specific autocrine, paracrine and endocrine growth factors. A portion of this course will discuss the clinical and experimental data on the production and interaction of those cytokines and cell systems considered to be critical to tissue damage. It had long been suggested that interindividual differences in radiation-induced normal tissue damage was genetically regulated, at least in part. Both clinical and experimental data supported this hypothesis but it is the recent advances in human and mouse molecular genetics which have provided the tools to dissect out the genetic component of normal tissue damage. These data will be presented and related to the potential to develop genetic markers to identify sensitive individuals. The impact on clinical outcome of the ability to identify prospectively sensitive patients will be discussed. Clinically it is well-accepted that the volume of tissue irradiated is a critical factor in determining tissue damage. A profusion of mathematical models for estimating dose-volume relationships in a number of organs have been published recently despite the fact that little data are available to support these models. This course will review the

  13. Review of RBE values of 15 MeV neutrons for effects on normal tissues

    NARCIS (Netherlands)

    Broerse, J.J.

    1974-01-01

    Values of the relative biological effectiveness (RBE) of fast neutrons for effect on normal tissue depend not only on the neutron energy and the dose, but also on the type of tissue irradiated. Values of the RBE of 15 MeV neutrons are reviewed for rapidly proliferating rodent tissue, such as mouse

  14. Human normal tissue reactions in radiotherapy

    International Nuclear Information System (INIS)

    Taniike, Keiko

    1990-01-01

    Acute and late normal tissue reactions in radiotherapy have not been considered to be major problems with conventional fractionation. But they may cause certain problems when newer schedules such as hyperfractionation or accelerated fractionation are used. In opposing parallel radiotherapy, the dose fractionation of skin or subcutaneous connective tissue are different between in one portal and two portals daily. So we examined acute skin erythema and late connective tissue fibrosis in the two groups (one and two portals) of the patients with uterus cancer. Acute skin erythema and late connective tissue fibrosis were slightly stronger in case of one portal daily. In relation to the anatomical site of skin, acute skin erythema was stronger at the buttocks than the lower abdomen, but late fibrosis was reverse to that. So the degree of acute skin erythema did not predict the degree of late connective tissue fibrosis. The number of Time Dose Fractionation Factor could roughly estimate the degree of erythema and fibrosis. Late fibrosis in 36 fractions increased with an increase of abdominal thickness, but acute erythema did not. (author)

  15. Normal tissue complication probability for salivary glands

    International Nuclear Information System (INIS)

    Rana, B.S.

    2008-01-01

    The purpose of radiotherapy is to make a profitable balance between the morbidity (due to side effects of radiation) and cure of malignancy. To achieve this, one needs to know the relation between NTCP (normal tissue complication probability) and various treatment variables of a schedule viz. daily dose, duration of treatment, total dose and fractionation along with tissue conditions. Prospective studies require that a large number of patients be treated with varied schedule parameters and a statistically acceptable number of patients develop complications so that a true relation between NTCP and a particular variable is established. In this study Salivary Glands Complications have been considered. The cases treated in 60 Co teletherapy machine during the period 1994 to 2002 were analyzed and the clinicians judgement in ascertaining the end points was the only means of observations. The only end points were early and late xerestomia which were considered for NTCP evaluations for a period of 5 years

  16. DNA Double-Strand Break Rejoining in Complex Normal Tissues

    International Nuclear Information System (INIS)

    Ruebe, Claudia E.; Dong, Xiaorong; Kuehne, Martin; Fricke, Andreas; Kaestner, Lars; Lipp, Peter; Ruebe, Christian

    2008-01-01

    Purpose: The clinical radiation responses of different organs vary widely and likely depend on the intrinsic radiosensitivities of their different cell populations. Double-strand breaks (DSBs) are the most deleterious form of DNA damage induced by ionizing radiation, and the cells' capacity to rejoin radiation-induced DSBs is known to affect their intrinsic radiosensitivity. To date, only little is known about the induction and processing of radiation-induced DSBs in complex normal tissues. Using an in vivo model with repair-proficient mice, the highly sensitive γH2AX immunofluorescence was established to investigate whether differences in DSB rejoining could account for the substantial differences in clinical radiosensitivity observed among normal tissues. Methods and Materials: After whole body irradiation of C57BL/6 mice (0.1, 0.5, 1.0, and 2.0 Gy), the formation and rejoining of DSBs was analyzed by enumerating γH2AX foci in various organs representative of both early-responding (small intestine) and late-responding (lung, brain, heart, kidney) tissues. Results: The linear dose correlation observed in all analyzed tissues indicated that γH2AX immunofluorescence allows for the accurate quantification of DSBs in complex organs. Strikingly, the various normal tissues exhibited identical kinetics for γH2AX foci loss, despite their clearly different clinical radiation responses. Conclusion: The identical kinetics of DSB rejoining measured in different organs suggest that tissue-specific differences in radiation responses are independent of DSB rejoining. This finding emphasizes the fundamental role of DSB repair in maintaining genomic integrity, thereby contributing to cellular viability and functionality and, thus, tissue homeostasis

  17. T lymphocytes and normal tissue responses to radiation

    International Nuclear Information System (INIS)

    Schaue, Dörthe; McBride, William H.

    2012-01-01

    There is compelling evidence that lymphocytes are a recurring feature in radiation damaged normal tissues, but assessing their functional significance has proven difficult. Contradictory roles have been postulated in both tissue pathogenesis and protection, although these are not necessarily mutually exclusive as the immune system can display what may seem to be opposing faces at any one time. While the exact role of T lymphocytes in irradiated normal tissue responses may still be obscure, their accumulation after tissue damage suggests they may be critical targets for radiotherapeutic intervention and worthy of further study. This is accentuated by recent findings that pathologically damaged “self,” such as occurs after exposure to ionizing radiation, can generate danger signals with the ability to activate pathways similar to those that activate adoptive immunity to pathogens. In addition, the demonstration of T cell subsets with their recognition radars tuned to “self” moieties has revolutionized our ideas on how all immune responses are controlled and regulated. New concepts of autoimmunity have resulted based on the dissociation of immune functions between different subsets of immune cells. It is becoming axiomatic that the immune system has the power to regulate radiation-induced tissue damage, from failure of regeneration to fibrosis, to acute and chronic late effects, and even to carcinogenesis. Our understanding of the interplay between T lymphocytes and radiation-damaged tissue may still be rudimentary but this is a good time to re-examine their potential roles, their radiobiological and microenvironmental influences, and the possibilities for therapeutic manipulation. This review will discuss the yin and yang of T cell responses within the context of radiation exposures, how they might drive or protect against normal tissue side effects and what we may be able do about it.

  18. Technique for sparing previously irradiated critical normal structures in salvage proton craniospinal irradiation

    International Nuclear Information System (INIS)

    McDonald, Mark W; Wolanski, Mark R; Simmons, Joseph W; Buchsbaum, Jeffrey C

    2013-01-01

    Cranial reirradiation is clinically appropriate in some cases but cumulative radiation dose to critical normal structures remains a practical concern. The authors developed a simple technique in 3D conformal proton craniospinal irradiation (CSI) to block organs at risk (OAR) while minimizing underdosing of adjacent target brain tissue. Two clinical cases illustrate the use of proton therapy to provide salvage CSI when a previously irradiated OAR required sparing from additional radiation dose. The prior radiation plan was coregistered to the treatment planning CT to create a planning organ at risk volume (PRV) around the OAR. Right and left lateral cranial whole brain proton apertures were created with a small block over the PRV. Then right and left lateral “inverse apertures” were generated, creating an aperture opening in the shape of the area previously blocked and blocking the area previously open. The inverse aperture opening was made one millimeter smaller than the original block to minimize the risk of dose overlap. The inverse apertures were used to irradiate the target volume lateral to the PRV, selecting a proton beam range to abut the 50% isodose line against either lateral edge of the PRV. Together, the 4 cranial proton fields created a region of complete dose avoidance around the OAR. Comparative photon treatment plans were generated with opposed lateral X-ray fields with custom blocks and coplanar intensity modulated radiation therapy optimized to avoid the PRV. Cumulative dose volume histograms were evaluated. Treatment plans were developed and successfully implemented to provide sparing of previously irradiated critical normal structures while treating target brain lateral to these structures. The absence of dose overlapping during irradiation through the inverse apertures was confirmed by film. Compared to the lateral X-ray and IMRT treatment plans, the proton CSI technique improved coverage of target brain tissue while providing the least

  19. Potential clinical impact of normal-tissue intrinsic radiosensitivity testing

    International Nuclear Information System (INIS)

    Bentzen, Soeren M.

    1997-01-01

    assays may be as a guide for the prescription of treatment schedules that are costly or involves a high risk of complications. Examples of this are certain strategies attempting to widen the therapeutic window, the use of very high doses or re-irradiation of a previously irradiated region, or the selection of patients for experimental strategies like the use of biological response modifiers to reduce normal-tissue toxicity. Finally, published data are summarized on the possible correlation between the radiosensitivities of tumor and normal tissues or between the sensitivities of various normal tissues

  20. Radioprotection of normal tissues of the mouse by hypoxic breathing

    International Nuclear Information System (INIS)

    Stevens, G.N.; Joiner, B.; Denekamp, J.

    1989-01-01

    Hypoxic breathing during irradiation has been advocated as a therapeutic modality, to increase the efficacy of radiotherapy. In this form of treatment, the total and daily X-ray dose is increased by a factor of 1.25, on the assumption that all normal tissues in the beam will be protected to a similar extent by breathing gas containing a reduced oxygen concentration (usually 10%). To test this concept, we have determined the effect of varying the inspired oxygen tension on the radiosensitivity of 3 normal tissues in the mouse (kidney, jejunum and skin), and have compared these results with data from the literature for mouse lung. Reduction of the inspired oxygen tension from 21% (air) to 7-8% led to much greater radioprotection of skin (protection factor 1.37) than of lung (1.09). Protection factors for jejunum and kidney were 1.16 and 1.36 respectively. The results show that the extent of radioprotection afforded by hypoxic breathing is tissue dependent, and that great care must be taken clinically in choosing the increased radiation dose to be used in conjunction with hypoxic breathing

  1. Canine tumor and normal tissue response to heat and radiation

    International Nuclear Information System (INIS)

    Gillette, E.L.; McChesney, S.L.

    1985-01-01

    Oral squamous cell carcinomas of dogs were treated with either irradiation alone or combined with hyperthermia. Tumor control was assessed as no evidence of disease one year following treatment. Dogs were randomized to variable radiation doses which were given in ten fractions three times a week for three weeks. Heat was given three hours after the first and third radiation dose each week for seven treatments. The attempt was made to achieve a minimum tumor temperature of 42 0 C for thirty minutes with a maximum normal tissue temperature of 40 0 C. It was usually possible to selectively heat tumors. The TCD 50 for irradiation alone was about 400 rads greater than for heat plus irradiation. The dose response curve for heat plus radiation was much steeper than for radiation alone indicating less heterogeneity of tumor response. That also implies a much greater effectiveness of radiation combined with heat at higher tumor control probabilities. Early necrosis caused by heating healed with conservative management. No increase in late radiation necrosis was observed

  2. The role of irradiated tissue during pattern formation in the regenerating limb

    International Nuclear Information System (INIS)

    Maden, M.

    1979-01-01

    The amphibian limb regeneration blastema is used here to examine whether irradiated, non-dividing tissue can participate in the development of new patterns of morphogenesis. Irradiated blastemas were rotated 180 0 on normal stumps and normal blastemas rotated on irradiated stumps. In both cases supernumerary elements developed from the unirradiated tissue. The supernumeraries were defective but this did not seem to be due to a lack of tissue. Rather it suggested that this could be a realization of compartments in vertebrate development or simply reflect the limited regulative ability of the blastema. The results are also discussed in relation to a recent model of pattern formation. (author)

  3. Options and pitfalls of normal tissues complication probability models

    International Nuclear Information System (INIS)

    Dorr, Wolfgang

    2011-01-01

    Full text: Technological improvements in the physical administration of radiotherapy have led to increasing conformation of the treatment volume (TV) with the planning target volume (PTV) and of the irradiated volume (IV) with the TV. In this process of improvement of the physical quality of radiotherapy, the total volumes of organs at risk exposed to significant doses have significantly decreased, resulting in increased inhomogeneities in the dose distributions within these organs. This has resulted in a need to identify and quantify volume effects in different normal tissues. Today, irradiated volume today must be considered a 6t h 'R' of radiotherapy, in addition to the 5 'Rs' defined by Withers and Steel in the mid/end 1980 s. The current status of knowledge of these volume effects has recently been summarized for many organs and tissues by the QUANTEC (Quantitative Analysis of Normal Tissue Effects in the Clinic) initiative [Int. J. Radiat. Oncol. BioI. Phys. 76 (3) Suppl., 2010]. However, the concept of using dose-volume histogram parameters as a basis for dose constraints, even without applying any models for normal tissue complication probabilities (NTCP), is based on (some) assumptions that are not met in clinical routine treatment planning. First, and most important, dose-volume histogram (DVH) parameters are usually derived from a single, 'snap-shot' CT-scan, without considering physiological (urinary bladder, intestine) or radiation induced (edema, patient weight loss) changes during radiotherapy. Also, individual variations, or different institutional strategies of delineating organs at risk are rarely considered. Moreover, the reduction of the 3-dimentional dose distribution into a '2dimensl' DVH parameter implies that the localization of the dose within an organ is irrelevant-there are ample examples that this assumption is not justified. Routinely used dose constraints also do not take into account that the residual function of an organ may be

  4. Intensity modulated radiotherapy and 3D conformal radiotherapy for whole breast irradiation: a comparative dosimetric study and introduction of a novel qualitative index for plan evaluation, the normal tissue index

    Energy Technology Data Exchange (ETDEWEB)

    Yim, Jackie; Suttie, Clare; Bromley, Regina; Morgia, Marita; Lamoury, Gillian [Department of Radiation Oncology, Royal North Shore Hospital, St Leonards, New South Wales (Australia)

    2015-09-15

    We report on a retrospective dosimetric study, comparing 3D conformal radiotherapy (3DCRT) and hybrid intensity modulated radiotherapy (hIMRT). We evaluated plans based on their planning target volume coverage, dose homogeneity, dose to organs at risk (OARs) and exposure of normal tissue to radiation. The Homogeneity Index (HI) was used to assess the dose homogeneity in the target region, and we describe a new index, the normal tissue index (NTI), to assess the dose in the normal tissue inside the tangent treatment portal. Plans were generated for 25 early-stage breast cancer patients, using a hIMRT technique. These were compared with the 3DCRT plans of the treatment previously received by the patients. Plan quality was evaluated using the HI, NTI and dose to OARs. The hIMRT technique was significantly more homogenous than the 3DCRT technique, while maintaining target coverage. The hIMRT technique was also superior at minimising the amount of tissue receiving D{sub 105%} and above (P < 0.0001). The ipsilateral lung and contralateral breast maximum were significantly lower in the hIMRT plans (P < 0.05 and P < 0.005), but the 3DCRT technique achieved a lower mean heart dose in left-sided breast cancer patients (P < 0.05). Hybrid intensity modulated radiotherapy plans achieved improved dose homogeneity compared to the 3DCRT plans and superior outcome with regard to dose to normal tissues. We propose that the addition of both HI and NTI in evaluating the quality of intensity modulated radiotherapy (IMRT) breast plans provides clinically relevant comparators which more accurately reflect the new paradigm of treatment goals and outcomes in the era of breast IMRT.

  5. Intensity modulated radiotherapy and 3D conformal radiotherapy for whole breast irradiation: a comparative dosimetric study and introduction of a novel qualitative index for plan evaluation, the normal tissue index

    International Nuclear Information System (INIS)

    Yim, Jackie; Suttie, Clare; Bromley, Regina; Morgia, Marita; Lamoury, Gillian

    2015-01-01

    We report on a retrospective dosimetric study, comparing 3D conformal radiotherapy (3DCRT) and hybrid intensity modulated radiotherapy (hIMRT). We evaluated plans based on their planning target volume coverage, dose homogeneity, dose to organs at risk (OARs) and exposure of normal tissue to radiation. The Homogeneity Index (HI) was used to assess the dose homogeneity in the target region, and we describe a new index, the normal tissue index (NTI), to assess the dose in the normal tissue inside the tangent treatment portal. Plans were generated for 25 early-stage breast cancer patients, using a hIMRT technique. These were compared with the 3DCRT plans of the treatment previously received by the patients. Plan quality was evaluated using the HI, NTI and dose to OARs. The hIMRT technique was significantly more homogenous than the 3DCRT technique, while maintaining target coverage. The hIMRT technique was also superior at minimising the amount of tissue receiving D 105% and above (P < 0.0001). The ipsilateral lung and contralateral breast maximum were significantly lower in the hIMRT plans (P < 0.05 and P < 0.005), but the 3DCRT technique achieved a lower mean heart dose in left-sided breast cancer patients (P < 0.05). Hybrid intensity modulated radiotherapy plans achieved improved dose homogeneity compared to the 3DCRT plans and superior outcome with regard to dose to normal tissues. We propose that the addition of both HI and NTI in evaluating the quality of intensity modulated radiotherapy (IMRT) breast plans provides clinically relevant comparators which more accurately reflect the new paradigm of treatment goals and outcomes in the era of breast IMRT

  6. EPR study of the reactions of tumour and normal tissues under ionizing radiation

    International Nuclear Information System (INIS)

    Rikhireva, G.T.; Pulatova, M.K.; Turganov, M.M.; Pal'mina, N.P.; Burlakova, E.B.

    1978-01-01

    Data on the EPR spectrum characteristics of irradiated tissues of tumour-free animals and animals with tumour are presented. Mice of the Csub(3)Hsub(A) line were used in the experiments. Hepatoma was subcutaneously transplanted with the suspension of tumour tissue reduced to fragments. Animals were killed in 6-8 days after transplantation and in the case of tumour-free animals liver was immediately isolated while in the case of animals with tumour isolated were liver and tumour. Tissues cut with scissors were frozen in liquid nitrogen. Tissue samples were exposed to 60 Co at 1 Mrad dose and -196 deg C. On the base of the data it has been concluded: firstly, there are differences between the EPR spectra of normal and tumour tissue samples irradiated at -196 deg C. Asymmetryc signal with Δ H=Ge and g=2.0005 (''tumour signal'') is typical only for the EPR spectra of tumour and liver tissues of the animal with tumour. Thus, in the -author's opinion, irradiation use turns out to be useful for detecting the difference between the normal and tumour tissues. Secondly, ''tumour signal'' intensity changes after ionol incorporation into animal organism, used as a modificator of tissue sensitivity to the irradiation effect

  7. The influence of dose fractionation and dose rate on normal tissue responses

    International Nuclear Information System (INIS)

    Barendsen, G.W.

    1982-01-01

    An analysis of responses of a variety of normal tissues in animals to fractionated irradiations has been made with the aim of developing a formalism for the prediction of tolerance doses as a function of the dose per fraction and the overall treatment time. An important feature of the formalism is that it is directly based on radiological insights and therefore provides a logical concept to account for the diversity of tissue responses. (Auth.)

  8. Statistical validation of normal tissue complication probability models

    NARCIS (Netherlands)

    Xu, Cheng-Jian; van der Schaaf, Arjen; van t Veld, Aart; Langendijk, Johannes A.; Schilstra, Cornelis

    2012-01-01

    PURPOSE: To investigate the applicability and value of double cross-validation and permutation tests as established statistical approaches in the validation of normal tissue complication probability (NTCP) models. METHODS AND MATERIALS: A penalized regression method, LASSO (least absolute shrinkage

  9. Computer modeling the boron compound factor in normal brain tissue

    International Nuclear Information System (INIS)

    Gavin, P.R.; Huiskamp, R.; Wheeler, F.J.; Griebenow, M.L.

    1993-01-01

    The macroscopic distribution of borocaptate sodium (Na 2 B 12 H 11 SH or BSH) in normal tissues has been determined and can be accurately predicted from the blood concentration. The compound para-borono-phenylalanine (p-BPA) has also been studied in dogs and normal tissue distribution has been determined. The total physical dose required to reach a biological isoeffect appears to increase directly as the proportion of boron capture dose increases. This effect, together with knowledge of the macrodistribution, led to estimates of the influence of the microdistribution of the BSH compound. This paper reports a computer model that was used to predict the compound factor for BSH and p-BPA and, hence, the equivalent radiation in normal tissues. The compound factor would need to be calculated for other compounds with different distributions. This information is needed to design appropriate normal tissue tolerance studies for different organ systems and/or different boron compounds

  10. Pathologic evaluation of normal and perfused term placental tissue

    DEFF Research Database (Denmark)

    Maroun, Lisa Leth; Mathiesen, Line; Hedegaard, Morten

    2014-01-01

    This study reports for the 1st time the incidence and interobserver variation of morphologic findings in a series of 34 term placentas from pregnancies with normal outcome used for perfusion studies. Histologic evaluation of placental tissue is challenging, especially when it comes to defining...... "normal tissue" versus "pathologic lesions." A scoring system for registration of abnormal morphologic findings was developed. Light microscopic examination was performed independently by 2 pathologists, and interobserver variation was analyzed. Findings in normal and perfused tissue were compared...... and selected findings were tested against success parameters from the perfusions. Finally, the criteria for frequent lesions with fair to poor interobserver variation in the nonperfused tissue were revised and reanalyzed. In the perfused tissue, the perfusion artefact "trophoblastic vacuolization," which...

  11. Comparative study of radiosensitivity of normal and regenerating tissues

    International Nuclear Information System (INIS)

    Samokhvalova, H.S.; Popova, M.F.

    1983-01-01

    A comparative study of radiosensitivity of cells of normal and regenerating tissues of bone marrow and spleen has demonstrated that single exposure to X-rays produces a lesser damaging effect on regenerating tissues than on normal ones. The data obtained indicate that the increase in radioresistance of the organism during active regeneration of the haemopoietic organs is due not merely to the increase in the dividing cell pool of these organs but also to qualitative changes in their functional state

  12. Immunolocalization of transforming growth factor alpha in normal human tissues

    DEFF Research Database (Denmark)

    Christensen, M E; Poulsen, Steen Seier

    1996-01-01

    anchorage-independent growth of normal cells and was, therefore, considered as an "oncogenic" growth factor. Later, its immunohistochemical presence in normal human cells as well as its biological effects in normal human tissues have been demonstrated. The aim of the present investigation was to elucidate...... the distribution of the growth factor in a broad spectrum of normal human tissues. Indirect immunoenzymatic staining methods were used. The polypeptide was detected with a polyclonal as well as a monoclonal antibody. The polyclonal and monoclonal antibodies demonstrated almost identical immunoreactivity. TGF......-alpha was found to be widely distributed in cells of normal human tissues derived from all three germ layers, most often in differentiated cells. In epithelial cells, three different kinds of staining patterns were observed, either diffuse cytoplasmic, cytoplasmic in the basal parts of the cells, or distinctly...

  13. Lipid metabolism in rat tissues exposed to the chronic effects of γ-irradiation and ubiquinone Q9

    International Nuclear Information System (INIS)

    Novoselova, E.G.

    1992-01-01

    Chronic γ-irradiation of rats with the daily dose of 0.129 Gy activates the synthesis of various classes of lipids in the thymus, spleen and bone marrow cells and induces lipid accumulation in these tissues. Feeding of rats with the antioxidant, ubiquinone Q-9, under conditions of chronic irradiation causes a considerable normalization of lipogenesis and levels of the lipid concentration in the tissues of animals irradiated with the dose of 20 Gy

  14. Evaluation of normal tissue responses to high-LET radiations

    International Nuclear Information System (INIS)

    Halnan, K.E.

    1979-01-01

    Clinical results presented have been analysed to evaluate normal tissue responses to high-LET radiations. Damage to brain, spinal cord, gut, skin, connective tissue and bone has occurred. A high RBE is probable for brain and possible for spinal cord and gut but other reasons for damage are also discussed. A net gain seems likely. Random controlled trials are advocated. (author)

  15. Radiation-induced hypoxia may perpetuate late normal tissue injury

    International Nuclear Information System (INIS)

    Vujaskovic, Zeljko; Anscher, Mitchell S.; Feng, Q.-F.; Rabbani, Zahid N.; Amin, Khalid; Samulski, Thaddeus S.; Dewhirst, Mark W.; Haroon, Zishan A.

    2001-01-01

    Purpose: The purpose of this study was to determine whether or not hypoxia develops in rat lung tissue after radiation. Methods and Materials: Fisher-344 rats were irradiated to the right hemithorax using a single dose of 28 Gy. Pulmonary function was assessed by measuring the changes in respiratory rate every 2 weeks, for 6 months after irradiation. The hypoxia marker was administered 3 h before euthanasia. The tissues were harvested at 6 weeks and 6 months after irradiation and processed for immunohistochemistry. Results: A moderate hypoxia was detected in the rat lungs at 6 weeks after irradiation, before the onset of functional or histopathologic changes. The more severe hypoxia, that developed at the later time points (6 months) after irradiation, was associated with a significant increase in macrophage activity, collagen deposition, lung fibrosis, and elevation in the respiratory rate. Immunohistochemistry studies revealed an increase in TGF-β, VEGF, and CD-31 endothelial cell marker, suggesting a hypoxia-mediated activation of the profibrinogenic and proangiogenic pathways. Conclusion: A new paradigm of radiation-induced lung injury should consider postradiation hypoxia to be an important contributing factor mediating a continuous production of a number of inflammatory and fibrogenic cytokines

  16. Effect of 60Co-irradiation on normal and low protein diet fed rat brain

    International Nuclear Information System (INIS)

    Hasan, S.S.; Habibullah, M.

    1980-01-01

    The effect of whole-body irradiation (Co-60) on the brain tissue in Holtzmann strain adult male rats was studied. Two doses of irradiation (450 R,950 R) were tried on animals which were fed on normal as well as low protein diets over a period of 10 generations. In the normal rats, 450 R initially caused a lowered total protein. DNA and RNA content in the brain. After 7 days a tendency towards normalcy was observed. In the 950 R irradiated normal rats the diminution of protein content appeared irreversible. In malnourished 450 R irradiated rats, the protein content rose less steeply over the 7 days of observation. A higher dose of 950 R enhanced this effect on protein and also lowered the DNA content on day 5. The RNA content in the 950 R group with malnutrition showed a marked increase towards or beyond control perhaps as an expression of uncoupled feedback control. The paper gives evidence that protein deficiency may interfere with cellular regeneration in irradiated brain. (orig.) [de

  17. Effect of /sup 60/Co-irradiation on normal and low protein diet fed rat brain

    Energy Technology Data Exchange (ETDEWEB)

    Hasan, S S [Garhwal Univ., Srinagar, Uttar Pradesh (India). Dept. of Zoology; Habibullah, M [Jawaharlal Nehru Univ., New Delhi (India). Neurobiology Lab.

    1980-06-01

    The effect of whole-body irradiation (Co-60) on the brain tissue in Holtzmann strain adult male rats was studied. Two doses of irradiation (450 R,950 R) were tried on animals which were fed on normal as well as low protein diets over a period of 10 generations. In the normal rats, 450 R initially caused a lowered total protein. DNA and RNA content in the brain. After 7 days a tendency towards normalcy was observed. In the 950 R irradiated normal rats the diminution of protein content appeared irreversible. In malnourished 450 R irradiated rats, the protein content rose less steeply over the 7 days of observation. A higher dose of 950 R enhanced this effect on protein and also lowered the DNA content on day 5. The RNA content in the 950 R group with malnutrition showed a marked increase towards or beyond control perhaps as an expression of uncoupled feedback control. The paper gives evidence that protein deficiency may interfere with cellular regeneration in irradiated brain.

  18. Radiogenic responses of normal cells induced by fractionated irradiation -a simulation study. Pt. 2. Late responses

    International Nuclear Information System (INIS)

    Duechting, W.; Ulmer, W.; Ginsberg, T.; Kikhounga-N'Got, O.; Saile, C.

    1995-01-01

    Based on controlled theory, a computed simulation model has been constructed which describes the time course of slowly responding normal cells after irradiation exposure. Subsequently, different clinical irradiation schemes are compared in regard to their delayed radiogenic responses referred to as late effects in radiological terminology. A cybernetic model of a paraenchymal tissue consisting of dominantly resting functional cells has been developed and transferred into a computer model. The radiation effects are considered by characteristic cell parameters as well as by the linear-quadratic model. Three kinds of tissue (brain and lung parenchym of the mouse, liver parenchym of rat) have been irradiated in the model according to standard-, super-, hyperfractionation and a single high dose per week. The simulation studies indicate that the late reaction of brain parenchym to hyperfractionation (3 x 1.5 Gy per day) and of lung parenchym tissue with regard to all fractionation schemes applied is particularly severe. The behavior of liver parenchym is not unique. A comparison of the simulation results basing to the survival of cell numbers with clinical experience and practice shows that the clinical reality can qualitatively be represented by the model. This opens the door for connecting side effects to normal tissue with the corresponding tumor efficacy (discussed in previous papers). The model is open to further refinement and to discussions referring to the phenomenon of late effects. (orig.) [de

  19. The In Vitro Response of Tissue Stem Cells to Irradiation With Different Linear Energy Transfers

    NARCIS (Netherlands)

    Nagle, Peter W; Hosper, Nynke A; Ploeg, Emily M; van Goethem, Marc-Jan; Brandenburg, Sytze; Langendijk, Johannes A; Chiu, Roland K; Coppes, Robert P

    2016-01-01

    PURPOSE: A reduction in the dose, irradiated volume, and sensitivity of, in particular, normal tissue stem cells is needed to advance radiation therapy. This could be obtained with the use of particles for radiation therapy. However, the radiation response of normal tissue stem cells is still an

  20. Cell and tissue kinetics of the subependymal layer in mouse brain following heavy charged particle irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Manley, N.B.; Fabrikant, J.I.; Alpen, E.L.

    1988-12-01

    The following studies investigate the cellular response and cell population kinetics of the subependymal layer in the mouse brain exposed to heavy charged particle irradiation. Partial brain irradiation with helium and neon ions was confined to one cortex of the brain. Both the irradiated and the unirradiated contralateral cortex showed similar disturbances of the cell and tissue kinetics in the subependymal layers. The irradiated hemisphere exhibited histological damage, whereas the unirradiated side appeared normal histologically. This study concerns the cell population and cell cycle kinetics of the subependymal layer in the mouse brain, and the effects of charged particle irradiations on this cell population. Quantitative high resolution autoradiography was used to study the kinetic parameters in this cell layer. This study should help in understanding the effects of these high-energy heavy ions on normal mammalian brain tissue. The response of the mammalian brain exposure to charged particle ionizing radiation may be extremely variable. It varies from minimal physiological changes to overt tissue necrosis depending on a number of factors such as: the administered dose, dose-rate, the volume of the irradiated tissue, and the biological end-point being examined.

  1. High and Low LET Radiation Differentially Induce Normal Tissue Damage Signals

    International Nuclear Information System (INIS)

    Niemantsverdriet, Maarten; Goethem, Marc-Jan van; Bron, Reinier; Hogewerf, Wytse; Brandenburg, Sytze; Langendijk, Johannes A.; Luijk, Peter van; Coppes, Robert P.

    2012-01-01

    Purpose: Radiotherapy using high linear energy transfer (LET) radiation is aimed at efficiently killing tumor cells while minimizing dose (biological effective) to normal tissues to prevent toxicity. It is well established that high LET radiation results in lower cell survival per absorbed dose than low LET radiation. However, whether various mechanisms involved in the development of normal tissue damage may be regulated differentially is not known. Therefore the aim of this study was to investigate whether two actions related to normal tissue toxicity, p53-induced apoptosis and expression of the profibrotic gene PAI-1 (plasminogen activator inhibitor 1), are differentially induced by high and low LET radiation. Methods and Materials: Cells were irradiated with high LET carbon ions or low LET photons. Cell survival assays were performed, profibrotic PAI-1 expression was monitored by quantitative polymerase chain reaction, and apoptosis was assayed by annexin V staining. Activation of p53 by phosphorylation at serine 315 and serine 37 was monitored by Western blotting. Transfections of plasmids expressing p53 mutated at serines 315 and 37 were used to test the requirement of these residues for apoptosis and expression of PAI-1. Results: As expected, cell survival was lower and induction of apoptosis was higher in high -LET irradiated cells. Interestingly, induction of the profibrotic PAI-1 gene was similar with high and low LET radiation. In agreement with this finding, phosphorylation of p53 at serine 315 involved in PAI-1 expression was similar with high and low LET radiation, whereas phosphorylation of p53 at serine 37, involved in apoptosis induction, was much higher after high LET irradiation. Conclusions: Our results indicate that diverse mechanisms involved in the development of normal tissue damage may be differentially affected by high and low LET radiation. This may have consequences for the development and manifestation of normal tissue damage.

  2. Normal tissue tolerance to external beam radiation therapy: Peripheral nerves

    International Nuclear Information System (INIS)

    Henriques de Figueiredo, B.; Dejean, C.; Sargos, P.; Kantor, G.; Huchet, A.; Mamou, N.; Loiseau, H.

    2010-01-01

    Plexopathies and peripheral neuropathies appear progressively and with several years delay after radiotherapy. These lesions are observed principally after three clinical situations: supraclavicular and axillar irradiations for breast cancer, pelvic irradiations for various pathologies and limb irradiations for soft tissue sarcomas. Peripheral nerves and plexus (brachial and lumbosacral) are described as serial structures and are supposed to receive less than a given maximum dose linked to the occurrence of late injury. Literature data, mostly ancient, define the maximum tolerable dose to a threshold of 60 Gy and highlight also a great influence of fractionation and high fraction doses. For peripheral nerves, most frequent late effects are pain with significant differences of occurrence between 50 and 60 Gy. At last, associated pathologies (diabetes, vascular pathology, neuropathy) and associated treatments have probably to be taken into account as additional factors, which may increase the risk of these late radiation complications. (authors)

  3. Normal tissue dose-effect models in biological dose optimisation

    International Nuclear Information System (INIS)

    Alber, M.

    2008-01-01

    Sophisticated radiotherapy techniques like intensity modulated radiotherapy with photons and protons rely on numerical dose optimisation. The evaluation of normal tissue dose distributions that deviate significantly from the common clinical routine and also the mathematical expression of desirable properties of a dose distribution is difficult. In essence, a dose evaluation model for normal tissues has to express the tissue specific volume effect. A formalism of local dose effect measures is presented, which can be applied to serial and parallel responding tissues as well as target volumes and physical dose penalties. These models allow a transparent description of the volume effect and an efficient control over the optimum dose distribution. They can be linked to normal tissue complication probability models and the equivalent uniform dose concept. In clinical applications, they provide a means to standardize normal tissue doses in the face of inevitable anatomical differences between patients and a vastly increased freedom to shape the dose, without being overly limiting like sets of dose-volume constraints. (orig.)

  4. A compendium of canine normal tissue gene expression.

    Directory of Open Access Journals (Sweden)

    Joseph Briggs

    Full Text Available BACKGROUND: Our understanding of disease is increasingly informed by changes in gene expression between normal and abnormal tissues. The release of the canine genome sequence in 2005 provided an opportunity to better understand human health and disease using the dog as clinically relevant model. Accordingly, we now present the first genome-wide, canine normal tissue gene expression compendium with corresponding human cross-species analysis. METHODOLOGY/PRINCIPAL FINDINGS: The Affymetrix platform was utilized to catalogue gene expression signatures of 10 normal canine tissues including: liver, kidney, heart, lung, cerebrum, lymph node, spleen, jejunum, pancreas and skeletal muscle. The quality of the database was assessed in several ways. Organ defining gene sets were identified for each tissue and functional enrichment analysis revealed themes consistent with known physio-anatomic functions for each organ. In addition, a comparison of orthologous gene expression between matched canine and human normal tissues uncovered remarkable similarity. To demonstrate the utility of this dataset, novel canine gene annotations were established based on comparative analysis of dog and human tissue selective gene expression and manual curation of canine probeset mapping. Public access, using infrastructure identical to that currently in use for human normal tissues, has been established and allows for additional comparisons across species. CONCLUSIONS/SIGNIFICANCE: These data advance our understanding of the canine genome through a comprehensive analysis of gene expression in a diverse set of tissues, contributing to improved functional annotation that has been lacking. Importantly, it will be used to inform future studies of disease in the dog as a model for human translational research and provides a novel resource to the community at large.

  5. Reirradiation of normal tissues: Preclinical radiobiological data; Reirradiation des tissus sains: donnees radiobiologiques precliniques

    Energy Technology Data Exchange (ETDEWEB)

    Bourgier, C.; Vozenin, M.C.; Deutsch, E. [Departement de radiotherapie et laboratoire Upres EA2710, institut Gustave-Roussy, 94 - Villejuif (France)

    2010-10-15

    Reirradiation represent an unfrequent particular clinical situation. The risk/benefit ratio assessment must be taken into account, considering both clinical and dosimetric aspects. There is a relatively limited amount of preclinical data available to date and clinicians should cautiously perform re-irradiations in selected indications. This review summarizes the experimental data available on reirradiation of normal tissues, the consequences on early and late toxicities as well as the intrinsic limitations of these models. (authors)

  6. Integral dose and evaluation of irradiated tissue volume

    International Nuclear Information System (INIS)

    Sivachenko, T.P.; Kalina, V.K.; Belous, A.K.; Gaevskij, V.I.

    1984-01-01

    Two parameters having potentialities of radiotherapy planning improvement are under consideration. One of these two parameters in an integral dose. An efficiency of application of special tables for integral dose estimation is noted. These tables were developed by the Kiev Physician Improvement Institute and the Cybernetics Institute of the Ukrainian SSR Academy of Science. The meaning of the term of ''irradiated tissue volume'' is specified, and the method of calculation of the irradiated tissue effective mass is considered. It is possible to evaluate with higher accuracy tolerance doses taking into account the irradiated mass

  7. Response of tissue lysosomes in Gamma-irradiated rats and possible modulation through diclofenac treatment

    International Nuclear Information System (INIS)

    Hassan, S.H.S.; Abu-Ghadeer, A.R.M.; Osman, S.A.A.

    1995-01-01

    The effect of pre and post-irradiation treatment of rats with diclofenac (5 mg kg-1) for modulating the damaging effect of radiation on tissue lysosomes was investigated. The parameters used for this study were the activity level of acid phosphatase (ACP) and acid ribonuclease (RNase) activities, both being hydrolytic enzymes of lysosomes. The activities of ACP and RNase in liver, spleen, intestine, kidney, lung and brain were determined at different times up to 14 days after irradiation (4(Gy). Lysosomal affection was represented by time dependent significant increase in ACP activity in all the tissue homogenates of the investigated organs 3, 7 and 14 days after irradiation at 4 Gy. Gamma irradiation at 4 Gy resulted also in a significant rise in RNase activity of all the tissue organs 3 days post-irradiation. However, gradual decrease in the enzyme activity was recorded 7 and 14 days following irradiation. Diclofenac, pre (as prophylactic) and post (as therapeutic) irradiation treatment of rats successfully restored the increase in the enzymatic activities of ACP and RNase nearly to their normal levels in all the investigated organs. The beneficial effect of diclofenac inhibited completely the effect of irradiation at 14 days post-exposure. 2 figs., 2 tabs

  8. Effect of whole body irradiation on different tissues

    International Nuclear Information System (INIS)

    Casati, V.; Nardino, A.; Tomassi, I.; Becciolini, A.; Rizzi, M.; Martelli, T.

    1979-01-01

    The uptake and elimination of 14 C leucine were analysed in controls and in rats irradiated 2 h before injection with 8 Gy whole-body irradiation. Plasma, small intestine, kidney and skin were assayed after homogenization for TCA soluble and insoluble activity curves. In highly differentiated tissues with poor proliferative activity and low protein turnover, the uptake and elimination of the tracer did not appear to be affected by irradiation. In the small intestine differences between control and irradiated animals seemed significant. (Auth.)

  9. Radiation-induced normal tissue damage: implications for radiotherapy

    International Nuclear Information System (INIS)

    Prasanna, Pataje G.

    2014-01-01

    Radiotherapy is an important treatment modality for many malignancies, either alone or as a part of combined modality treatment. However, despite technological advances in physical treatment delivery, patients suffer adverse effects from radiation therapy due to normal tissue damage. These side effects may be acute, occurring during or within weeks after therapy, or intermediate to late, occurring months to years after therapy. Minimizing normal tissue damage from radiotherapy will allow enhancement of tumor killing and improve tumor control and patients quality of life. Understanding mechanisms through which radiation toxicity develops in normal tissue will facilitate the development of next generation radiation effect modulators. Translation of these agents to the clinic will also require an understanding of the impact of these protectors and mitigators on tumor radiation response. In addition, normal tissues vary in radiobiologically important ways, including organ sensitivity to radiation, cellular turnover rate, and differences in mechanisms of injury manifestation and damage response. Therefore, successful development of radiation modulators may require multiple approaches to address organ/site-specific needs. These may include treatments that modify cellular damage and death processes, inflammation, alteration of normal flora, wound healing, tissue regeneration and others, specifically to counter cancer site-specific adverse effects. Further, an understanding of mechanisms of normal tissue damage will allow development of predictive biomarkers; however harmonization of such assays is critical. This is a necessary step towards patient-specific treatment customization. Examples of important adverse effects of radiotherapy either alone or in conjunction with chemotherapy, and important limitations in the current approaches of using radioprotectors for improving therapeutic outcome will be highlighted. (author)

  10. Tissue glycogen and blood glucose in irradiated rats. II

    International Nuclear Information System (INIS)

    Ahlersova, E.; Ahlers, I.; Praslicka, M.

    1980-01-01

    Male rats of the Wistar strain were continuously irradiated with 0.57 Gy (60 R) of gamma rays from a 60 Co source. Irradiation lasted from 1 to 50 days in an experimental field where also control animals shielded from radiation were placed. After a 16 h starvation, the concentration of glucose in the blood and of glycogen in the liver and the heart was determined 1, 3, 7, 14, 21, 25, 32, 39 and 50 days after the beginning of irradiation. The concentration of blood glucose in irradiated rats did not practically differ from that of control animals during the whole period of investigation. The concentration of liver glycogen in irradiated animals was higher than that in the controls during all time intervals, except for day 1. The values of glycogen in the heart muscle were approximately identical in the irradiated and control rats, except for day 21 when they sharply increased in the irradiated animals. In addition to the investigation of blood glucose and tissue glycogen during continuous irradiation, these parameters were studied immediately, and 1, 6 and 12 months after continuous irradiation with a daily exposure of 0.57 Gy (60 R) up to a total exposure of 14.35 Gy (1500 R) of gamma rays. Considerably higher values of liver glycogen were detected in the irradiated rats immediately, and 1 and 6 months after the end of irradiation. (author)

  11. Measurement of human normal tissue and tumour responses

    International Nuclear Information System (INIS)

    Ross, G.; Yarnold, J.R.

    1988-01-01

    The scarcity of quantitative measures of normal tissue damage and tumour response in patients undergoing radiotherapy is an obstacle to the clinical evaluation of new treatment strategies. Retrospective studies of complications in critical normal tissues taught important lessons in the past concerning the potential dangers of hypofractionation. However, it is unethical to use serious complications as planned end-points in prospective studies. This paper reviews the desirable characteristics of clinical end-points required to compare alternative treatments employing radiotherapy, with emphasis on simple scales applied by clinicians or even the patients themselves

  12. Effect of irradiation on glycosaminoglycans connect in rat tissue

    Energy Technology Data Exchange (ETDEWEB)

    Drozdz, M; Kucharz, E; Glowacki, A; Zylka, J

    1981-01-01

    Glycosaminoglycan (GAGs) fractions were determined in tissues (skin, liver, lungs, aortic wall) and blood serum of rats irradiated with a single dose of 500 R. An increase of total GAGs as well as changes in the fractions were found in the tissues and urine of exposed rats.

  13. Late effects of normal tissues (lent) scoring system: the soma scale

    International Nuclear Information System (INIS)

    Mornex, F.; Pavy, J.J.; Denekamp, J.

    1997-01-01

    Radiation tolerance of normal tissues remains the limiting factor for delivering tumoricidal dose. The late toxicity of normal tissues is the most critical element of an irradiation: somatic, functional and structural alterations occur during the actual treatment itself, but late effects manifest months to years after acute effects heal, and may progress with time. The optimal therapeutic ratio ultimately requires not only complete tumor clearance, but also minimal residual injury to surrounding vital normal tissues. The disparity between the intensity of acute and late effects and the inability to predict the eventual manifestation of late normal tissue injury has made radiation oncologists recognize the importance of careful patient follow-up. There is so far no uniform toxicity scoring system to compare several clinical studies in the absence of a 'common toxicity language'. This justifies the need to establish a precise evaluation system for the analysis of late effects of radiation on normal tissues. The SOMA/LENT scoring system results from an international collaboration. European Organization Treatment of Cancer (EORTC) and Radiation Therapy Oncology Group (RTOG) have created subcommittees with the aim of addressing the question of standardized toxic effects criteria. This effort appeared as a necessity to standardize and improve the data recording, to then describe and evaluate uniform toxicity at regular time intervals. The current proposed scale is not yet validated, and should be used cautiously. (authors)

  14. Differentiating cancerous from normal breast tissue by redox imaging

    Science.gov (United States)

    Xu, He N.; Tchou, Julia; Feng, Min; Zhao, Huaqing; Li, Lin Z.

    2015-02-01

    Abnormal metabolism can be a hallmark of cancer occurring early before detectable histological changes and may serve as an early detection biomarker. The current gold standard to establish breast cancer (BC) diagnosis is histological examination of biopsy. Previously we have found that pre-cancer and cancer tissues in animal models displayed abnormal mitochondrial redox state. Our technique of quantitatively measuring the mitochondrial redox state has the potential to be implemented as an early detection tool for cancer and may provide prognostic value. We therefore in this present study, investigated the feasibility of quantifying the redox state of tumor samples from 16 BC patients. Tumor tissue aliquots were collected from both normal and cancerous tissue from the affected cancer-bearing breasts of 16 female patients (5 TNBC, 9 ER+, 2 ER+/Her2+) shortly after surgical resection. All specimens were snap-frozen with liquid nitrogen on site and scanned later with the Chance redox scanner, i.e., the 3D cryogenic NADH/oxidized flavoprotein (Fp) fluorescence imager. Our preliminary results showed that both NADH and Fp (including FAD, i.e., flavin adenine dinucleotide) signals in the cancerous tissues roughly tripled to quadrupled those in the normal tissues (pcancerous tissues than in the normal ones (pcancer and non-cancer breast tissues in human patients and this novel redox scanning procedure may assist in tissue diagnosis in freshly procured biopsy samples prior to tissue fixation. We are in the process of evaluating the prognostic value of the redox imaging indices for BC.

  15. Telomere length in normal and neoplastic canine tissues.

    Science.gov (United States)

    Cadile, Casey D; Kitchell, Barbara E; Newman, Rebecca G; Biller, Barbara J; Hetler, Elizabeth R

    2007-12-01

    To determine the mean telomere restriction fragment (TRF) length in normal and neoplastic canine tissues. 57 solid-tissue tumor specimens collected from client-owned dogs, 40 samples of normal tissue collected from 12 clinically normal dogs, and blood samples collected from 4 healthy blood donor dogs. Tumor specimens were collected from client-owned dogs during diagnostic or therapeutic procedures at the University of Illinois Veterinary Medical Teaching Hospital, whereas 40 normal tissue samples were collected from 12 control dogs. Telomere restriction fragment length was determined by use of an assay kit. A histologic diagnosis was provided for each tumor by personnel at the Veterinary Diagnostic Laboratory at the University of Illinois. Mean of the mean TRF length for 44 normal samples was 19.0 kilobases (kb; range, 15.4 to 21.4 kb), and the mean of the mean TRF length for 57 malignant tumors was 19.0 kb (range, 12.9 to 23.5 kb). Although the mean of the mean TRF length for tumors and normal tissues was identical, tumor samples had more variability in TRF length. Telomerase, which represents the main mechanism by which cancer cells achieve immortality, is an attractive therapeutic target. The ability to measure telomere length is crucial to monitoring the efficacy of telomerase inhibition. In contrast to many other mammalian species, the length of canine telomeres and the rate of telomeric DNA loss are similar to those reported in humans, making dogs a compelling choice for use in the study of human anti-telomerase strategies.

  16. Biochemical and Tissue Studies on Post Irradiation Recovery in Mammals

    International Nuclear Information System (INIS)

    Abdou, M.I.M.

    2004-01-01

    three main studies were performed in this thesis, namely, mortality and survival study, biochemical studies, and studies on tissue alterations cobalt-60 gamma irradiation for low let was used for the external whole body irradiation of the irradiated animal groups. a total number of animals of 722 virgin female adult wister rats of approximately the same age and weight were used for the three studies that were performed, including the control and irradiated animal groups. the animals were housed and kept with special care at fixed temperature, humidity and diet. the study on mortality and survival included 370 animals divided into control and groups irradiated with 4,5,6,7,8 and 9 Gy. this study was followed up for one year to record the number and date of animal deaths for the different irradiated groups. for the 8 and 9 Gy irradiated groups the follow up ended after 12 weeks and 11 days respectively when animal mortality reached 100%. the maximum percent mortality was noted at the second week (3.3,8,14 and 29%) for the 4,5,6 and 7 Gy irradiated groups respectively. for the 8 and 9 Gy irradiated groups, the maximum percent mortality was noted at the first week (42.9 and 90% respectively). regression equations were applied for the percent of mortality of the 5-8 Gy irradiated groups to estimate the LD 50/30, which was found to be 6.4 Gy

  17. MRI appearance of radiation-induced changes of normal cervical tissues

    International Nuclear Information System (INIS)

    Noemayr, A.; Lell, M.; Bautz, W.; Sweeney, R.; Lukas, P.

    2001-01-01

    Irradiation causes specific MRI changes in anatomic morphology and signal intensity. To avoid misinterpretation, it is important to consider the potential radiation changes of normal tissue in MRI. The aim of this study was to describe the detected radiation effects on normal cervical tissues in MRI. Pretreatment and posttreatment MRI of 52 patients with primary neck tumors were evaluated retrospectively. The MR imaging was performed before initiating radiotherapy and at the end of the treatment period. Patients underwent follow-up studies within 24 months after the end of irradiation. Edema was the main radiation-induced effect. It was detected in the epiglottis, larynx, pharynx wall, retro- and parapharyngeal space, salivary glands, muscles, and subcutaneous tissue. In some cases the bone marrow of the mandible showed edema, due to osteonecrosis. We additionally detected fluid accumulation in the mastoid cells. Radiation caused volume reduction of the parotid gland, thickening of the pharynx wall, and fatty degeneration of bone marrow. Magnetic resonance imaging is an excellent method of depicting radiation-induced changes of normal tissue. Especially T2-weighted sequences allow the detection of even slight edema. It is important to be aware of the most common radiation-induced changes in MRI and to take them into account when assessing an examination. (orig.)

  18. Genetic markers for prediction of normal tissue toxicity after radiotherapy

    DEFF Research Database (Denmark)

    Alsner, Jan; Andreassen, Christian Nicolaj; Overgaard, Jens

    2008-01-01

    During the last decade, a number of studies have supported the hypothesis that there is an important genetic component to the observed interpatient variability in normal tissue toxicity after radiotherapy. This review summarizes the candidate gene association studies published so far on the risk...

  19. A prospective three-dimensional analysis about the impact of differences in the clinical target volume in prostate cancer irradiation on normal-tissue exposure. A potential for increasing the benefit/risk ratio

    International Nuclear Information System (INIS)

    Hille, A.; Toews, N.; Schmidberger, H.; Hess, C.F.

    2005-01-01

    Background and purpose: rectal toxicity following external-beam irradiation of prostate cancer correlates with the exposed percentage of rectal volume. Recently, it has been recommended to reduce the volume of the seminal vesicles that should be included in the clinical target volume (CTV). The purpose of this study was to quantitatively assess the impact of this CTV reduction on the expected rectal and bladder dose sparing. Patients and methods: 14 patients with localized prostate cancer undergoing external-beam radiotherapy were investigated. The prostate, the prostate + entire seminal vesicles, or the prostate + proximal seminal vesicles were delineated as CTV. Treatment plans were generated and compared concerning rectum and bladder dose-volume histograms (DVHs). Results: the exposure of rectum and bladder volume was significantly lower in case of irradiation of the prostate only compared to inclusion of the proximal or entire seminal vesicles into the CTV. The reduction of the CTV from prostate + entire seminal vesicles to prostate + proximal seminal vesicles led to a significant reduction of the rectal and bladder dose exposure. Conclusion: reduction of the CTV to the prostate only, or to the prostate + proximal seminal vesicles led to significant rectal and bladder dose sparing compared to irradiation of the prostate + entire seminal vesicles. In patients with a higher risk for seminal vesicles involvement, irradiation of the prostate + proximal seminal vesicles should be preferred. In case of a need for irradiation of the entire seminal vesicles, patients should be informed about a higher risk for chronic rectal toxicity and, possibly, for bladder complications. (orig.)

  20. Radiosensitization effects of nicotinamide on malignant and normal mouse tissue

    International Nuclear Information System (INIS)

    Jonsson, G.G.; Kjellen, E.; Pero, R.W.; Cameron, R.

    1985-01-01

    Inhibitors of the chromatin-associated enzyme adenosine diphosphate ribosyltransferase have been found to inhibit DNA strand rejoining and to potentiate lethality of DNA-damaging agents both in vivo and in vitro. The authors have in this work examined the radiosensitizing potential of one such inhibitor, nicotinamide, on tumor tissue by using transplanted C3H mouse mammary adenocarcinomas and on normal tissue in a tail-stunting experiment using BALB/cA mice. The data indicate a radiosensitizing effect of nicotinamide on tumor cells as well as on normal tissue. The data indicate a possible role of adenosine diphosphate ribosyltransferase inhibitors as a sensitizing agent in the radiotherapy of malignant tumors

  1. Photoacoustic spectroscopic differences between normal and malignant thyroid tissues

    Science.gov (United States)

    Li, Li; Xie, Wengming; Li, Hui

    2012-12-01

    The thyroid is one of the main endocrine glands of human body, which plays a crucial role in the body's metabolism. Thyroid cancer mortality ranks only second to ovarian cancer in endocrine cancer. Routine diagnostic methods of thyroid diseases in present clinic exist misdiagnosis and missed diagnosis to varying degrees. Those lead to miss the best period of cancer treatment--early. Photoacoustic spectroscopy technology is a new tool, which provides an effective and noninvasive way for biomedical materials research, being highly sensitive and without sample pretreatment. In this paper, we use photoacoustic spectroscopy technology (PAST) to detect the absorption spectrum between normal and malignant thyroid tissues. The result shows that the photoacoustic spectroscopy technology (PAST) could differentiate malignant thyroid tissue from normal thyroid tissue very well. This technique combined with routine diagnostic methods has the potential to increase the diagnostic accuracy in clinical thyroid cancer diagnosis.

  2. The effects of vascularized tissue transfer on re-irradiation

    International Nuclear Information System (INIS)

    Narayan, K.; Ashton, M.W.; Taylor, G.I.

    1996-01-01

    Purpose: Nowadays, radical re-irradiation of locally recurrent squamous cell carcinoma is being increasingly tried. The process usually involves some form of surgical excision and vascularized tissue transfer followed by re-irradiation. The aim of this study was to examine the extent of protection from the effects of re-irradiation provided by vascularized tissue transfer. Methods and Materials: One hundred Sprague Dawley rats had their left thighs irradiated to a total dose of 72Gy in 8 fractions, one fraction per day, 5 days per week. The rats were then divided into two groups: At 4 months, one half of the rats had 50% of their quadriceps musculature excised and replaced with a vascularized non-irradiated rectus abdominous myocutaneous flap. The other group served as the control. Six months following the initial radiotherapy all rats were then re-irradiated with either 75 or 90% of the original dose. Incidence of necrosis and the extent of necrosis was measured. Microvasculature of control, transplanted muscle and recipient site was studied by micro-corrosion cast technique and histology of cast specimen. tissues were sampled at pre-irradiation and at 2, 6 and 12 months post re-irradiation. Microvascular surface area was measured from the histology of cast specimen. Results: Necrosis in the control group was clinically evident at 6 weeks post re irradiation and by 10 months all rats developed necrosis. Forty per cent of the thigh that received 75% of the original dose on re-irradiation did not develop any necrosis by 13 months. Other groups developed necrosis to variable extents, however a rim of tissue around the graft always survived. The average thickness of surviving tissue was 9mm. (range being 4-25 mm). None of the transferred flap nor re-irradiated recipient quadriceps developed necrosis. Conclusion: 1. Transplanted rectus abdominus myocutaneous flap and undisturbed muscle have similar radiation tolerance. 2. Vascularized myocutaneous flap offers

  3. Optical-Thermal Response of Laser-Irradiated Tissue

    CERN Document Server

    Welch, Ashley J

    2011-01-01

    The second edition of 'Optical-Thermal Response of Laser-Irradiated Tissue' maintains the standard of excellence established in the first edition, while adjusting the content to reflect changes in tissue optics and medical applications since 1995. The material concerning light propagation now contains new chapters devoted to electromagnetic theory for coherent light. The material concerning thermal laser-tissue interactions contains a new chapter on pulse ablation of tissue. The medical applications section now includes several new chapters on Optical Coherent Tomography, acoustic imaging, molecular imaging, forensic optics and nerve stimulation. A detailed overview is provided of the optical and thermal response of tissue to laser irradiation along with diagnostic and therapeutic examples including fiber optics. Sufficient theory is included in the book so that it is suitable for a one or two semester graduate or for senior elective courses. Material covered includes: 1. light propagation and diagnostic appl...

  4. Identification of molecular mechanisms of radiation-induced vascular damage in normal tissues using microarray analyses

    International Nuclear Information System (INIS)

    Kruse, J.J.C.M.; Te Poele, J.A.M.; Russell, N.S.; Boersma, L.J.; Stewart, F.A.

    2003-01-01

    Radiation-induced telangiectasia, characterized by thin-walled dilated blood vessels, can be a serious late complication in patients that have been previously treated for cancer. It might cause cosmetic problems when occurring in the skin, and excessive bleeding requiring surgery when occurring in rectal mucosa. The mechanisms underlying the development of radiation-induced telangiectasia are unclear. The aim of the present study is to determine whether microarrays are useful for studying mechanisms of radiation-induced telangiectasia. The second aim is to test the hypotheses that telangiectasia is characterized by a final common pathway in different tissues. Microarray experiments were performed using amplified RNA from (sham)irradiated mouse tissues (kidney, rectum) at different intervals (1-30 weeks) after irradiation. After normalization procedures, the differentially expressed genes were identified. Control/repeat experiments were done to confirm that the observations were not artifacts of the array procedure. The mouse kidney experiments showed significant upregulation of 31 and 42 genes and downregulation of 9 and 4 genes at 10 and 20 weeks after irradiation, respectively. Irradiated mouse rectum has 278 upregulated and 537 downregulated genes at 10 weeks and 86 upregulated and 29 downregulated genes at 20 weeks. During the development of telangiectasia, 19 upregulated genes and 5 downregulated genes were common to both tissues. Upregulation of Jagged-1, known to play a role in angiogenesis, is particularly interesting in the context of radiation-induced telangiectasia. Microarrays are affective discovery tools to identify novel genes of interest, which may be involved in radiation-induced normal tissue injury. Using information from control arrays (particularly straight color, color reverse and self-self experiments) allowed for a more accurate and reproducible identification of differentially expressed genes than the selection of an arbitrary 2-fold change

  5. Qualitative dose response of the normal canine head to epithermal neutron irradiation with and without boron capture

    International Nuclear Information System (INIS)

    DeHaan, C.E.; Gavin, P.R.; Kraft, S.L.; Wheeler, F.J.; Atkinson, C.A.

    1992-01-01

    Boron Neutron Capture Therapy is being re-evaluated for the treatment of intracranial tumors. Prior to human clinical trials, determination of normal tissue tolerance is critical. Dogs were chosen as a large animal model for the following reasons. Dogs can be evaluated with advanced imaging, diagnostic and therapeutic modalities. Dogs are amenable to detailed neurologic examination and subtle behavioral changes are easily detected. Specifically, Labrador retrievers were chosen for their large body and head size. The dogs received varying doses of epithermal neutron irradiation and boron neutron capture irradiation using an epithermal neutron source. The dogs were closely monitored for up to one year post irradiation

  6. Radioprotection of normal tissues in tumor-bearing mice by troxerutin

    International Nuclear Information System (INIS)

    Maurya, D.K.; Salvi, V.P.; Krishnan Nair, C.K.

    2004-01-01

    The flavanoid derivative troxerutin, used clinically for treating venous disorders, protected biomembranes and cellular DNA against the deleterious effects of γ-radiation. The peroxidation of lipids (measured as thiobarbituric acid-reacting substances, or TBARS) in rat liver microsomal and mitochondrial membranes resulting from γ-irradiation up to doses of 500 Gy in vitro was prevented by 0.2 mM troxerutin. The administration of troxerutin (175 mg/kg body weight) to tumor-bearing mice by intraperitoneal (ip) one hour prior to 4 Gy whole-body γ-irradiation significantly decreased the radiation-induced peroxidation of lipids in tissues such as liver and spleen, but there was no reduction of lipid peroxidation in tumor. The effect of troxerutin in γ-radiation-induced DNA strand breaks in different tissues of tumor-bearing mice was studied by comet assay. The administration of troxerutin to tumor-bearing animals protected cellular DNA against radiation-induced strand breaks. This was evidenced from decreases in comet tail length, tail moment, and percent of DNA in the tails in cells of normal tissues such as blood leukocytes and bone marrow, and these parameters were not altered in cells of fibrosarcoma tumor. The results revealed that troxerutin could preferentially protect normal tissues against radiation-induced damages in tumor-bearing animals. (author)

  7. Function of skeletal muscle tissue formed after myoblast transplantation into irradiated mouse muscles.

    Science.gov (United States)

    Wernig, A; Zweyer, M; Irintchev, A

    2000-01-15

    1. Pretreatment of muscles with ionising radiation enhances tissue formation by transplanted myoblasts but little is known about the effects on muscle function. We implanted myoblasts from an expanded, male-donor-derived, culture (i28) into X-ray irradiated (16 Gy) or irradiated and damaged soleus muscles of female syngeneic mice (Balb/c). Three to 6 months later the isometric contractile properties of the muscles were studied in vitro, and donor nuclei were visualised in muscle sections with a Y chromosome-specific DNA probe. 2. Irradiated sham-injected muscles had smaller masses than untreated solei and produced less twitch and tetanic force (all by about 18 %). Injection of 106 myoblasts abolished these deficiencies and innervation appeared normal. 3. Cryodamage of irradiated solei produced muscle remnants with few (1-50) or no fibres. Additional myoblast implantation led to formation of large muscles (25 % above normal) containing numerous small-diameter fibres. Upon direct electrical stimulation, these muscles produced considerable twitch (53 % of normal) and tetanic forces (35 % of normal) but innervation was insufficient as indicated by weak nerve-evoked contractions and elevated ACh sensitivity. 4. In control experiments on irradiated muscles, reinnervation was found to be less complete after botulinum toxin paralysis than after nerve crush indicating that proliferative arrest of irradiated Schwann cells may account for the observed innervation deficits. 5. Irradiation appears to be an effective pretreatment for improving myoblast transplantation. The injected cells can even produce organised contractile tissue replacing whole muscle. However, impaired nerve regeneration limits the functional performance of the new muscle.

  8. Mouse genetic approaches applied to the normal tissue radiation response

    International Nuclear Information System (INIS)

    Haston, Christina K.

    2012-01-01

    The varying responses of inbred mouse models to radiation exposure present a unique opportunity to dissect the genetic basis of radiation sensitivity and tissue injury. Such studies are complementary to human association studies as they permit both the analysis of clinical features of disease, and of specific variants associated with its presentation, in a controlled environment. Herein I review how animal models are studied to identify specific genetic variants influencing predisposition to radiation-induced traits. Among these radiation-induced responses are documented strain differences in repair of DNA damage and in extent of tissue injury (in the lung, skin, and intestine) which form the base for genetic investigations. For example, radiation-induced DNA damage is consistently greater in tissues from BALB/cJ mice, than the levels in C57BL/6J mice, suggesting there may be an inherent DNA damage level per strain. Regarding tissue injury, strain specific inflammatory and fibrotic phenotypes have been documented for principally, C57BL/6 C3H and A/J mice but a correlation among responses such that knowledge of the radiation injury in one tissue informs of the response in another is not evident. Strategies to identify genetic differences contributing to a trait based on inbred strain differences, which include linkage analysis and the evaluation of recombinant congenic (RC) strains, are presented, with a focus on the lung response to irradiation which is the only radiation-induced tissue injury mapped to date. Such approaches are needed to reveal genetic differences in susceptibility to radiation injury, and also to provide a context for the effects of specific genetic variation uncovered in anticipated clinical association studies. In summary, mouse models can be studied to uncover heritable variation predisposing to specific radiation responses, and such variations may point to pathways of importance to phenotype development in the clinic.

  9. Repair in normal tissues and the possible relevance to radiotherapy

    International Nuclear Information System (INIS)

    Field, S.B.; Hornsey, S.

    1977-01-01

    Between each fraction in radiotherapy, there is repair and recovery of both normal and neoplastic tissues. Several different types of repair have been identified. Some relate specifically to the effect of changing the number of fractions and others to the overall treatment time. Each will be discussed and particular attention will be paid to slow repair phenomena which have recently been the subject of much interest. (orig.) [de

  10. Morphologic alterations in normal and neoplastic tissues following hyperthermia treatment

    International Nuclear Information System (INIS)

    Badylak, S.F.; Babbs, C.F.

    1984-01-01

    The sequential morphologic alterations in normal skeletal muscle in rats, Walker 256 tumors in rats, and transmissible venereal tumors (TVT) in dogs following microwave-induced hyperthermia (43 0 C and 45 0 for 20 minutes) were studied by light and electron microscopy. Normal muscle and Walker 256 tumors showed vascular damage at 5 minutes post-heating (PH), followed by suppuration and thrombosis at 6 and 48 hours PH, and by regeneration and repair at 7 days PH. Endothelial damage and parenchymal degeneration were present 5 minutes PH. Progressive ischemic injury occurred for at least 48 hours PH. Two hyperthermia treatments, separated by a 30 or 60 minute cooling interval, were applied to rats implanted with Walker 256 tumors. Increased selective heating of tumor tissue versus surrounding normal tissue, and increased intratumoral temperatures were found during the second hyperthermia treatment. Canine TVTs were resistant to hyperthermia damage. These results characterized the sequential morphologic alterations following hyperthermia treatment and showed that: 1) vascular damage contributed to the immediate and latent cytotoxic effects of hyperthermia, 2) selective heating occurred in the neoplastic tissue disrupted by prior heat treatment, and 3) not all neoplasms are responsive to hyperthermia treatment

  11. Cellular localization of peptide hydrolases in chicken embryo tissues and influence of gamma irradiation on their activity

    Energy Technology Data Exchange (ETDEWEB)

    Khristov, D; Marinopolski, G

    1975-01-01

    Studied was the influence of chicken embryo irradiation at 600 R and 1000 R gamma rays on the activity of tissue peptide hydrolases in mitochondrial-lysosomal, microsomal and supernatant (cell hyaloplasm) cell fractions. The investigation was performed 50 to 168 hours post irradiation. The wole tissue (of the whole embryo) was examined following irradiation of 4-day-old embryos whose liver, muscle and brain tissues were post irradiation examined on day 12 and 16 of incubation. Prior to treatment, the tissues were threfold rinsed with sucrose solution to eliminate proeinase inhibitors. Lysosome membranes were destroyed by adding 0.5 % desoxycholate. It was found that: Peptide hydrolase activity of mitochondrial-lysosomal cell fractions of tissues of whole 6-day chicken embryos is 4-5 times as high as that of cell hyaloplasm. Peptide hydrolase activity of mitochondrial-lysosomal fractions of liver tissues decreases on day 18 and 19 post incubation, while the same fraction of muscle and brain tissues shows high activity. Peptide hydrolase activity of microsomal fraction and of cell hyaloplasm rises during embryonal development and exceeds the activity of liver tissue mitochondrial fraction. Peptide hydrolase activity of mitochondrial-lysosomal fraction of tissue of whole 6-day-old embryos 50 hours post irradiation is higher than the activity of non-irradiated embryos. Later the activity of this fraction diminishes and on the 168 hr post irradiation it drops below the normal. Microsomal fraction and cell hyaloplasm activity likewise show deviation from the norm. Peptide hydrolase activity of mitochondrial-lysosomal fraction of liver, muscle and brain tissue of 14 and 18-day-old embryos is higher than the control 50 hours post irradiation and then declines. The activity of mitochondrial-lysosomal fraction of embryo brain tissue changes most strikingly on irradiation, while other brain cell fractions change less compared with liver and muscle fractions.

  12. Cellular localization of peptide hydrolases in chicken embryo tissues and influence of gamma irradiation on their activity

    International Nuclear Information System (INIS)

    Khristov, D.; Marinopolski, G.

    1975-01-01

    Studied was the influence of chicken embryo irradiation at 600 R and 1000 R gamma rays on the activity of tissue peptide hydrolases in mitochondrial-lysosomal, microsomal and supernatant (cell hyaloplasm) cell fractions. The investigation was performed 50 to 168 hours post irradiation. The wole tissue (of the whole embryo) was examined following irradiation of 4-day-old embryos whose liver, muscle and brain tissues were post irradiation examined on day 12 and 16 of incubation. Prior to treatment, the tissues were threfold rinsed with sucrose solution to eliminate proeinase inhibitors. Lysosome membranes were destroyed by adding 0.5 % desoxycholate. It was found that: Peptide hydrolase activity of mitochondrial-lysosomal cell fractions of tissues of whole 6-day chicken embryos is 4-5 times as high as that of cell hyaloplasm. Peptide hydrolase activity of mitochondrial-lysosomal fractions of liver tissues decreases on day 18 and 19 post incubation, while the same fraction of muscle and brain tissues shows high activity. Peptide hydrolase activity of microsomal fraction and of cell hyaloplasm rises during embryonal development and exceeds the activity of liver tissue mitochondrial fraction. Peptide hydrolase activity of mitochondrial-lysosomal fraction of tissue of whole 6-day-old embryos 50 hours post irradiation is higher than the activity of non-irradiated embryos. Later the activity of this fraction diminishes and on the 168 hr post irradiation it drops below the normal. Microsomal fraction and cell hyaloplasm activity likewise show deviation from the norm. Peptide hydrolase activity of mitochondrial-lysosomal fraction of liver, muscle and brain tissue of 14 and 18-day-old embryos is higher than the control 50 hours post irradiation and then declines. The activity of mitochondrial-lysosomal fraction of embryo brain tissue changes most strikingly on irradiation, while other brain cell fractions change less compared with liver and muscle fractions

  13. CURED I - LENT. Late effects of cancer treatment on normal tissues

    International Nuclear Information System (INIS)

    Rubin, P.; Okunieff, P.; Constine, L.S.; Rochester Univ. School of Medicine and Dentistry, Rochester, NY; Marks, L.B.

    2008-01-01

    The search for the most favorable therapeutic ratio - at which ablation of cancer is achieved while normal tissues are conserved - has been modern radiation oncology's equivalent of the quest for the Holy Grail. Our awareness of the late effects of radiation grew during the past century as new modalities were introduced. Heightened normal tissue reactions accompanied the higher rates of cancer ablation achieved by escalation of radiation doses, accelerated fractionated radiotherapy, and aggressive concurrent chemotherapy and radiation regimens. This volume is based on the LENT V NCI-sponsored meeting held in May 2004 and the CURED I conference held in 2006. Written by experts in the field, it addresses a number of critical topics relating to late effects, such as mechanisms of injury, the role of screening, options for interventions, second malignancies, and prevention. It is hoped that it will assist the reader in understanding how to prevent and treat the long-term side-effects of irradiation. (orig.)

  14. Tissue glycogen and blood glucose in irradiated rats. I

    International Nuclear Information System (INIS)

    Ahlersova, E.; Ahlers, I.; Paulikova, E.; Praslicka, M.

    1980-01-01

    Fed and starved (overnight) male rats of the Wistar strain were exposed to whole-body irradiation with 14.35 Gy (1500 R) of X-rays. After irradiation and sham-irradiation all animals were starved until examination performed 1, 6, 24, 48 and 72 h after treatment. The concentration of glucose in the blood and the concentration of glycogen in the liver, heart, skeletal muscle, brown and white adipose tissue were determined. The concentrations of blood glucose and liver glycogen were found to increase between 1 and 6 h after irradiation of the starved animals. The most pronounced increase in glycogen concentration in the liver and heart muscle was observed 24 and 48 h after irradiation. A similar increase in the concentration of blood glucose was found between 48 and 72 h after irradiation. The fed and starved irradiated rats reacted differently, particularly between 48 and 72 h; the liver glycogen concentration decreased in the fed animals and remained elevated in the starved ones. Very high values of terminal glycemia were observed in both groups. The accumulation of glycogen in the heart muscle indicates that this organ is sensitive to ionizing radiation. (author)

  15. On fibrinolytic phenomenon in the cancerous tissue of cervical carcinoma with special reference to irradiation changes

    International Nuclear Information System (INIS)

    Nakamura, Kazuyoshi

    1978-01-01

    In a study undertaken to investigate alterations of fibrinolytic enzymes in cancerous tissue of the cervix under radiotherapy, specimens were taken from malignant tissues of cervical cancer patients during irradiation therapy with Linac x-ray at 1000, 2000 and 3000 rads and were subsequently assayed for fibrinolytic enzyme activities using the fibrin plate method. No plasmin activity was demonstrable in the normal mucosa of the uterine cervix. Cancerous tissue of the uterine cervix also showed no demonstrable plasmin activity. The malignant tissue, as compared to the normal mucosa of the cervix, was found to have a lower activator activity, a higher proactivator activity and lower activities of both antiplasmin inhibitors. During radiotherapy for cervical cancer, plasmin activity was demonstrable in the cancerous tissue and in patients with malignant neoplasm, demonstrating that plasmin activity increased as the radiation dose was increased. A relationship seemed to exist between morphological changes and alterations in the fibrinolytic system of cancerous tissue of the cervix. From these findings it seems that the altered fibrinolytic enzyme system in cancerous tissue may have a close relationship with the growth and development of malignancy and may also have an important role in the occurrence of metastasis. There were some cases, in which an abnormal increase in activator activity occurred during irradiation therapy, leading to the death of the patients. This fact points to the possibility that activator activity might provide a useful index for evaluating the prognosis of cervical cancer. (author)

  16. Normal tissue tolerance to external beam radiation therapy: Adult bone; Dose de tolerance a l'irradiation des tissus sains: l'os chez l'adulte

    Energy Technology Data Exchange (ETDEWEB)

    Sargos, P.; Mamou, N.; Dejean, C.; Henriques de Figueiredo, B.; Kantor, G. [Departement de radiotherapie, Centre regional de lutte contre le cancer, institut Bergonie, 33 - Bordeaux (France); Huchet, A. [Departement de radiotherapie, hopital Saint-Andre, 33 - Bordeaux (France); Italiano, A. [Service d' oncologie medicale, Centre regional de lutte contre le cancer, institut Bergonie, 33 - Bordeaux (France)

    2010-07-15

    Radiation tolerance for bone tissue has been mostly evaluated with regard to bone fracture. Main circumstances are mandibula osteoradionecrosis, hip and costal fracture, and patent or radiologic fractures in the treated volume. After radiation therapy of bone metastasis, the analysis of related radiation fracture is difficult to individualize from a pathologic fracture. Frequency of clinical fracture is less than 5% in the large series or cohorts and is probably under-evaluated for the asymptomatic lesions. Women older than 50 years and with osteoporosis are probably the main population at risk. Dose-effect relations are difficult to qualify in older series. Recent models evaluating radiations toxicity on diaphysa suggest an important risk after 60 Gy, for high dose-fraction and for a large volume. (authors)

  17. The effects of irradiation on the periodontal tissues of rats with the low calcium diet

    International Nuclear Information System (INIS)

    Choi, Mun Cheol; Lee, Sang Rae

    1992-01-01

    The purpose of this study was to investigate the changes of periodontal tissues in the irradiated mandibular bone in rats which were fed normal diet and low calcium diet. In order to carry out this experiment, 64 seven-week old Sprague-Dawley strain rats weighing about 150 gms were selected and equally divided into one experimental group of 32 rats and one control group with the remainder. The experimental group and the control group were then subdivided into two groups when the rats reached the age of 10 weeks, 16 rats were allotted for each subdivided group was composed of 16 rats and exposed to irradiation. The two groups were irradiated a single dose of 20 Gy on the only jaw area and irradiated with a cobalt-60 teletherapy unit. The rats in the control and experimental groups were warily dissected by fours on the 3rd, 7th, the 14th, and the 21st day after irradiation. After each dissection, both sides of the dead rat mandibular bodies were removed and fixed with 10% neutral formalin. The specimens sectioned and observed in histopathological, histochemical, and immunocellular chemical methods. The obtained results were as follows: 1. In the mandibles of rats with low calcium diet the increased number of fibroblasts of periodontal ligaments, many small capillaries and irregular arrangement of loose collagen fibers were detected and the partial resorption of dentin and cementum could be found by the microscopic studies. 2. In the group of irradiated rats, deaerated periodontal tissues led to the condition of irregular arrangement of collagen fibers and the decreased number of fibroblasts. But this condition was somewhat restored after 21 days of experiment. 3. Periodontal tissues of the irradiated rat group with low calcium diet were destroyed earlier than those of the irradiated rat group with normal diet. Soon this condition was restored and then high cellularity and dense collagen fibers were observed. 4. Many periodontal cells bearing tumor necrosis factor

  18. The use of tissue culture techniques to detect irradiated vegetables

    International Nuclear Information System (INIS)

    Al-Safadi, B.; Sharabi, N.E.; Nabulsi, I

    2001-01-01

    the ability of two tissue culture methods, callus and vegetable growth induction, to detect irradiated vegetables was evaluated. Potato tubers, carrot roots, garlic cloves and onion bulbs were subjected to various gamma radiation doses (0, 25, 100, 150, 250, 500, 750, and 1000 Gy). Irradiated vegetables were cultured in vitro and in vivo (pots). Gamma irradiation significantly reduced callus-forming ability especially in carrot and potato where no callus was observed in doses higher than 50 Gy. Length of shoots and roots growing from irradiated garlic and onion explants was considerably reduced starting from the 25 Gy dose. No roots were formed on garlic explants at any irradiation dose. Garlic leaves growing from irradiated explants were spotted with purple to brown spots. The intensity of these spots increased as gamma ray dosage increased. In the pot experiment, potato plant appeared in the control only. On the contrary, a complete sprouting of garlic and onion was seen in all irradiation treatments. It was not possible to distinguish between the various irradiation treatments and the control 3 days after planting in pots. The two in vitro techniques, tested in our study, may effectively be used to detect irradiated vegetables and estimate the range of doses used. The callus formation method is more useful for potato and carrot, since regeneration of shoots in vitro from these two plants takes along time, making this method unpractical. The other technique is very useful in the case of onion and garlic since it is rapid. The two techniques can be used with most of the vegetables that can be cultured in vitro. (Author)

  19. Changes in lipolysis in rat adipose tissue during continuous irradiation

    International Nuclear Information System (INIS)

    Sedlakova, A.; Ahlers, I.; Praslicka, M.

    1980-01-01

    Changes in lipolysis were monitored by measuring the release of non-esterified fatty acids (NEFA) and glycerol under basal conditions and after stimulation with L-noradrenaline in rat adipose tissue in the course of continuous irradiation with daily gamma doses of 0.57 Gy (60 R) for 50 days. As compared with the control animals, lipolysis in the irradiated rats was lower on days 3 to 14, and higher on days 21 to 25 to 32 and at the end of the screening period (day 50) of continuous irradiation. The changes in lipolysis in the course of irradiation reflected individual stages of the general adaptation syndrome. Many changes were modified by the effect of non-specific factors due to the experimental field and the starvation prior to the analysis. Changes in lipolysis were connected with changes in the mobilization of fatty acids and the concentrations of NEFA in white adipose tissue with changes in serum lipids predominantly in the period of 21 to 25 days of continuous irradiation. (author)

  20. Radiosensitization In Vivo by Histone Deacetylase Inhibition with No Increase in Early Normal Tissue Radiation Toxicity.

    Science.gov (United States)

    Groselj, Blaz; Ruan, Jia-Ling; Scott, Helen; Gorrill, Jessica; Nicholson, Judith; Kelly, Jacqueline; Anbalagan, Selvakumar; Thompson, James; Stratford, Michael R L; Jevons, Sarah J; Hammond, Ester M; Scudamore, Cheryl L; Kerr, Martin; Kiltie, Anne E

    2018-02-01

    As the population ages, more elderly patients require radiotherapy-based treatment for their pelvic malignancies, including muscle-invasive bladder cancer, as they are unfit for major surgery. Therefore, there is an urgent need to find radiosensitizing agents minimally toxic to normal tissues, including bowel and bladder, for such patients. We developed methods to determine normal tissue toxicity severity in intestine and bladder in vivo , using novel radiotherapy techniques on a small animal radiation research platform (SARRP). The effects of panobinostat on in vivo tumor growth delay were evaluated using subcutaneous xenografts in athymic nude mice. Panobinostat concentration levels in xenografts, plasma, and normal tissues were measured in CD1-nude mice. CD1-nude mice were treated with drug/irradiation combinations to assess acute normal tissue effects in small intestine using the intestinal crypt assay, and later effects in small and large intestine at 11 weeks by stool assessment and at 12 weeks by histologic examination. In vitro effects of panobinostat were assessed by qPCR and of panobinostat, TMP195, and mocetinostat by clonogenic assay, and Western blot analysis. Panobinostat resulted in growth delay in RT112 bladder cancer xenografts but did not significantly increase acute (3.75 days) or 12 weeks' normal tissue radiation toxicity. Radiosensitization by panobinostat was effective in hypoxic bladder cancer cells and associated with class I HDAC inhibition, and protein downregulation of HDAC2 and MRE11. Pan-HDAC inhibition is a promising strategy for radiosensitization, but more selective agents may be more useful radiosensitizers clinically, resulting in fewer systemic side effects. Mol Cancer Ther; 17(2); 381-92. ©2017 AACR See all articles in this MCT Focus section, "Developmental Therapeutics in Radiation Oncology." ©2017 American Association for Cancer Research.

  1. A simple method to calculate the influence of dose inhomogeneity and fractionation in normal tissue complication probability evaluation

    International Nuclear Information System (INIS)

    Begnozzi, L.; Gentile, F.P.; Di Nallo, A.M.; Chiatti, L.; Zicari, C.; Consorti, R.; Benassi, M.

    1994-01-01

    Since volumetric dose distributions are available with 3-dimensional radiotherapy treatment planning they can be used in statistical evaluation of response to radiation. This report presents a method to calculate the influence of dose inhomogeneity and fractionation in normal tissue complication probability evaluation. The mathematical expression for the calculation of normal tissue complication probability has been derived combining the Lyman model with the histogram reduction method of Kutcher et al. and using the normalized total dose (NTD) instead of the total dose. The fitting of published tolerance data, in case of homogeneous or partial brain irradiation, has been considered. For the same total or partial volume homogeneous irradiation of the brain, curves of normal tissue complication probability have been calculated with fraction size of 1.5 Gy and of 3 Gy instead of 2 Gy, to show the influence of fraction size. The influence of dose distribution inhomogeneity and α/β value has also been simulated: Considering α/β=1.6 Gy or α/β=4.1 Gy for kidney clinical nephritis, the calculated curves of normal tissue complication probability are shown. Combining NTD calculations and histogram reduction techniques, normal tissue complication probability can be estimated taking into account the most relevant contributing factors, including the volume effect. (orig.) [de

  2. Variation in normal and tumor tissue sensitivity of mice to ionizing radiation-induced DNA strand breaks in vivo

    International Nuclear Information System (INIS)

    Meyn, R.E.; Jenkins, W.T.

    1983-01-01

    The efficiency of DNA strand break formation in normal and tumor tissues of mice was measured using the technique of alkaline elution coupled with a microfluorometric determination of DNA. This methodology allowed measurement of the DNA strand breaks produced in tissues irradiated in vivo with doses of radiation comparable to those used in radiotherapy (i.e., 1.0 gray) without the necessity for the cells to be dividing and incorporating radioactive precursors to label the DNA. The results showed that substantial differences existed among various tissues in terms of the amount of DNA strand break damage produced for a given dose of radiation. Of the normal tissues, the most breaks were produced in bone marrow and the least were produced in gut. Furthermore, strand break production was relatively inefficient in the tumor compared to the normal tissues. The efficiency of DNA strand break formation measured in the cells from the tissues irradiated in vitro was much more uniform and considerably greater than that measured in vivo, suggesting that the normal tissues in the animal may be radiobiologically hypoxic

  3. Trace element determinations in brain tissues from normal and clinically demented individuals

    International Nuclear Information System (INIS)

    Saiki, Mitiko; Genezini, Frederico A.; Leite, Renata E.P.; Grinberg, Lea T.; Ferretti, Renata E.L.; Suemoto, Claudia; Pasqualucci, Carlos A.; Jacob-Filho, Wilson

    2013-01-01

    Studies on trace element levels in human brains under normal and pathological conditions have indicated a possible correlation between some trace element concentrations and neurodegenerative diseases. In this study, analysis of brain tissues was carried out to investigate if there are any differences in elemental concentrations between brain tissues from a normal population above 50 years of age presenting Clinical Dementia Rating (CDR) equal to zero (CDR=0) and that cognitively affected population ( CDR=3). The tissues were dissected, ground, freeze-dried and then analyzed by instrumental neutron activation analysis. Samples and elemental standards were irradiated in a neutron flux at the IEA-R1 nuclear research reactor for Br, Fe, K, Na, Rb, Se and Zn determinations. The induced gamma ray activities were measured using a hyperpure Ge detector coupled to a gamma ray spectrometer. The one-way ANOVA test (p< 0.05) was used to compare the results. All the elements determined in the hippocampus brain region presented differences between the groups presenting CDR=0 and CDR=3. In the case of frontal region only the elements Na, Rb and Zn showed differences between these two groups. These findings proved the correlation between elemental levels present in brain tissues neurodegenerative diseases. Biological standard reference materials SRM 1566b Oyster Tissue and SRM 1577b Bovine Liver analyzed for quality control indicated good accuracy and precision of the results. (author)

  4. Effect of gamma irradiation at various temperatures and packaging conditions on chicken tissues

    International Nuclear Information System (INIS)

    Rady, A.H.; Maxwell, R.J.; Wierbicki, E.; Phillips, J.G.

    1988-01-01

    A lipid composition study on irradiated chicken muscle is reported. All muscle samples, packed either under air or vacuum, were gamma irradiated (-20 0 C) at 0, 1, 3, 6 and 10 kGy using 137 Cs (dose rate 0.1 kGy/min). Lipids were isolated from the muscle using a dry column extraction method with concomitant isolation of separated neutral and polar fractions. Lipid isolates were converted to their methyl esters and analyzed by capillary column gas chromatography with computer assisted data storage, followed by data consolidation and statistical computer analysis. Separated fatty acid profiles for neutral and polar lipids were obtained as normalized reports (each fatty acid as percentage of total fatty acids) and as gravimetric reports (mg of each fatty acid/100 g tissue). Normalized reports showed only negligible occurrence of significant changes in fatty acid profiles of neutral muscle lipid fractions regardless of irradiation doses (0 to 10 kGy) in either air and vacuum packaging. These differences were not apparent when the data were compiled as gravimetric reports. The polar lipid fractions containing the nutritionally significant ω3 and ω6 fatty acids showed only slight changes in normalized and gravimetric reports and were similarly unaffected with increasing levels of irradiation. Additionally, no new fatty acids or other artifacts due to gamma-irradiation were observed in detectable amounts by gas chromatography in any lipid fractions. (author)

  5. Lovastatin attenuates ionizing radiation-induced normal tissue damage in vivo

    International Nuclear Information System (INIS)

    Ostrau, Christian; Huelsenbeck, Johannes; Herzog, Melanie; Schad, Arno; Torzewski, Michael; Lackner, Karl J.; Fritz, Gerhard

    2009-01-01

    Background and purpose: HMG-CoA-reductase inhibitors (statins) are widely used lipid-lowering drugs. Moreover, they have pleiotropic effects on cellular stress responses, proliferation and apoptosis in vitro. Here, we investigated whether lovastatin attenuates acute and subchronic ionizing radiation-induced normal tissue toxicity in vivo. Materials and methods: Four hours to 24 h after total body irradiation (6 Gy) of Balb/c mice, acute pro-inflammatory and pro-fibrotic responses were analyzed. To comprise subchronic radiation toxicity, mice were irradiated twice with 2.5 Gy and analyses were performed 3 weeks after the first radiation treatment. Molecular markers of inflammation and fibrosis as well as organ toxicities were measured. Results: Lovastatin attenuated IR-induced activation of NF-κB, mRNA expression of cell adhesion molecules and mRNA expression of pro-inflammatory and pro-fibrotic marker genes (i.e. TNFα, IL-6, TGFβ, CTGF, and type I and type III collagen) in a tissue- and time-dependent manner. γH2AX phosphorylation stimulated by IR was not affected by lovastatin, indicating that the statin has no major impact on the induction of DNA damage in vivo. Radiation-induced thrombopenia was significantly alleviated by lovastatin. Conclusions: Lovastatin inhibits both acute and subchronic IR-induced pro-inflammatory and pro-fibrotic responses and cell death in normal tissue in vivo. Therefore, lovastatin might be useful for selectively attenuating acute and subchronic normal tissue damage caused by radiotherapy.

  6. Mathematical models of tumour and normal tissue response

    International Nuclear Information System (INIS)

    Jones, B.; Dale, R.G.; Charing Cross Group of Hospitals, London

    1999-01-01

    The historical application of mathematics in the natural sciences and in radiotherapy is compared. The various forms of mathematical models and their limitations are discussed. The Linear Quadratic (LQ) model can be modified to include (i) radiobiological parameter changes that occur during fractionated radiotherapy, (ii) situations such as focal forms of radiotherapy, (iii) normal tissue responses, and (iv) to allow for the process of optimization. The inclusion of a variable cell loss factor in the LQ model repopulation term produces a more flexible clonogenic doubling time, which can simulate the phenomenon of 'accelerated repopulation'. Differential calculus can be applied to the LQ model after elimination of the fraction number integers. The optimum dose per fraction (maximum cell kill relative to a given normal tissue fractionation sensitivity) is then estimated from the clonogen doubling times and the radiosensitivity parameters (or α/β ratios). Economic treatment optimization is described. Tumour volume studies during or following teletherapy are used to optimize brachytherapy. The radiation responses of both individual tumours and tumour populations (by random sampling 'Monte-Carlo' techniques from statistical ranges of radiobiological and physical parameters) can be estimated. Computerized preclinical trials can be used to guide choice of dose fractionation scheduling in clinical trials. The potential impact of gene and other biological therapies on the results of radical radiotherapy are testable. New and experimentally testable hypotheses are generated from limited clinical data by exploratory modelling exercises. (orig.)

  7. Cell and tissue kinetics of the subependymal layer in mouse brain following heavy charged particle irradiation

    International Nuclear Information System (INIS)

    Manley, N.B.

    1988-01-01

    The following studies investigate the cellular response and cell population kinetics of the subependymal layer in the mouse brain exposed to heavy charged particle irradiation. Partial brain irradiation with helium and neon ions was confined to one cortex of the brain. Both the irradiated and the unirradiated contralateral cortex showed similar disturbances of the cell and tissue kinetics in the subependymal layers. The irradiated hemisphere exhibited histological damage, whereas the unirradiated side appeared normal histologically. The decrease in the values of the labeling indices 1 week after charged particle irradiation was dose- and ion-dependent. Mitotic indices 1 week after 10 and 25 Gy helium and after 10 Gy neon were the same as those seen in the control mice. Analysis of cell kinetics 1 week after 10 Gy helium and 10 Gy neon irradiation suggests the presence of a progenitor subpopulation that is proliferating with a shorter cell cycle. Comparison of the responses to the different charged particle beams indicates that neon ions are more effective in producing direct cellular damage than the helium ions, but the surviving proliferating cells several divisions later continue to maintain active cell renewal. Based on the 1 week post-irradiation H 3 -TdR labeling indices, a rough estimate of the RBE for neon ions is at least 2.5 when compared to helium ions

  8. The use of normal tissue complication probability to predict radiation hepatitis

    International Nuclear Information System (INIS)

    Keum, Ki Chang; Seong, Jin Sil; Suh, Chang Ok; Lee, Sang Wook; Chung, Eun Ji; Shin, Hyun Soo; Kim, Gwi Eon

    2000-01-01

    Although it has been known that the tolerance of the liver to external beam irradiation depends on the irradiated volume and dose, few data exist which quantify this dependence. However, recently, with the development of three dimensional (3-D) treatment planning, have the tools to quantify the relationships between dose, volume, and normal tissue complications become available. The objective of this study is to investigate the relationships between normal tissue complication probability (NTCP) and the risk of radiation hepatitis for patients who received variant dose partial liver irradiation. From March 1992 to December 1994, 10 patients with hepatoma and 10 patients with bile duct cancer were included in this study. Eighteen patients had normal hepatic function, but 2 patients (prothrombin time 73%, 68%) had mild liver cirrhosis before irradiation. Radiation therapy was delivered with 10MV linear accelerator, 180-200 cGy fraction per day. The total dose ranged from 3,960 cGy to 6,000 cGy (median dose 5,040 cGy). The normal tissue complication probability was calculated by using Lyman's model. Radiation hepatitis was defined as the development of anicteric elevation of alkaline phosphatase of at least two fold and non-malignant ascites in the absence of documented progressive. The calculated NTCP ranged from 0.001 to 0.840 (median 0.05). Three of the 20 patients developed radiation hepatitis. The NTCP of the patients with radiation hepatitis were 0.390, 0.528, 0.844 (median: O.58±0.23), but that of the patients without radiation hepatitis ranged from 0.001 to 0.308 (median: 0.09±0.09). When the NTCP was calculated by using the volume factor of 0.32, a radiation hepatitis was observed only in patients with the NTCP value more than 0.39. By contrast, clinical results of evolving radiation hepatitis were not well correlated with NTCP value calculated when the volume factor of 0.69 was applied. On the basis of these observations, volume factor of 0.32 was more

  9. Mineral density volume gradients in normal and diseased human tissues.

    Directory of Open Access Journals (Sweden)

    Sabra I Djomehri

    Full Text Available Clinical computed tomography provides a single mineral density (MD value for heterogeneous calcified tissues containing early and late stage pathologic formations. The novel aspect of this study is that, it extends current quantitative methods of mapping mineral density gradients to three dimensions, discretizes early and late mineralized stages, identifies elemental distribution in discretized volumes, and correlates measured MD with respective calcium (Ca to phosphorus (P and Ca to zinc (Zn elemental ratios. To accomplish this, MD variations identified using polychromatic radiation from a high resolution micro-computed tomography (micro-CT benchtop unit were correlated with elemental mapping obtained from a microprobe X-ray fluorescence (XRF using synchrotron monochromatic radiation. Digital segmentation of tomograms from normal and diseased tissues (N=5 per group; 40-60 year old males contained significant mineral density variations (enamel: 2820-3095 mg/cc, bone: 570-1415 mg/cc, cementum: 1240-1340 mg/cc, dentin: 1480-1590 mg/cc, cementum affected by periodontitis: 1100-1220 mg/cc, hypomineralized carious dentin: 345-1450 mg/cc, hypermineralized carious dentin: 1815-2740 mg/cc, and dental calculus: 1290-1770 mg/cc. A plausible linear correlation between segmented MD volumes and elemental ratios within these volumes was established, and Ca/P ratios for dentin (1.49, hypomineralized dentin (0.32-0.46, cementum (1.51, and bone (1.68 were observed. Furthermore, varying Ca/Zn ratios were distinguished in adapted compared to normal tissues, such as in bone (855-2765 and in cementum (595-990, highlighting Zn as an influential element in prompting observed adaptive properties. Hence, results provide insights on mineral density gradients with elemental concentrations and elemental footprints that in turn could aid in elucidating mechanistic processes for pathologic formations.

  10. Mineral Density Volume Gradients in Normal and Diseased Human Tissues

    Science.gov (United States)

    Djomehri, Sabra I.; Candell, Susan; Case, Thomas; Browning, Alyssa; Marshall, Grayson W.; Yun, Wenbing; Lau, S. H.; Webb, Samuel; Ho, Sunita P.

    2015-01-01

    Clinical computed tomography provides a single mineral density (MD) value for heterogeneous calcified tissues containing early and late stage pathologic formations. The novel aspect of this study is that, it extends current quantitative methods of mapping mineral density gradients to three dimensions, discretizes early and late mineralized stages, identifies elemental distribution in discretized volumes, and correlates measured MD with respective calcium (Ca) to phosphorus (P) and Ca to zinc (Zn) elemental ratios. To accomplish this, MD variations identified using polychromatic radiation from a high resolution micro-computed tomography (micro-CT) benchtop unit were correlated with elemental mapping obtained from a microprobe X-ray fluorescence (XRF) using synchrotron monochromatic radiation. Digital segmentation of tomograms from normal and diseased tissues (N=5 per group; 40-60 year old males) contained significant mineral density variations (enamel: 2820-3095mg/cc, bone: 570-1415mg/cc, cementum: 1240-1340mg/cc, dentin: 1480-1590mg/cc, cementum affected by periodontitis: 1100-1220mg/cc, hypomineralized carious dentin: 345-1450mg/cc, hypermineralized carious dentin: 1815-2740mg/cc, and dental calculus: 1290-1770mg/cc). A plausible linear correlation between segmented MD volumes and elemental ratios within these volumes was established, and Ca/P ratios for dentin (1.49), hypomineralized dentin (0.32-0.46), cementum (1.51), and bone (1.68) were observed. Furthermore, varying Ca/Zn ratios were distinguished in adapted compared to normal tissues, such as in bone (855-2765) and in cementum (595-990), highlighting Zn as an influential element in prompting observed adaptive properties. Hence, results provide insights on mineral density gradients with elemental concentrations and elemental footprints that in turn could aid in elucidating mechanistic processes for pathologic formations. PMID:25856386

  11. Effect of endotoxin preparations (LPS) with irradiation decreased toxicity on the immune response of normal and irradiated rats

    Energy Technology Data Exchange (ETDEWEB)

    Elekes, E; Bertok, L [Orszagos Frederic Joliot-Curie Sugarbiologiai es Sugaregeszsegugyi Kutato Intezet, Budapest (Hungary)

    1979-03-01

    A comparison of the immunostimulating effect of parent and radiodetoxified with 50, 100, 150 and 200 kGy (5, 10, 15 and 20 Mrad) /sup 60/Co ..gamma..-rays endotoxin preparations in normal and irradiated rats is given. By increasing the dose of irradiation the immunostimulating effect decreased. The preparations detoxified even with the highest (200 kGy) dose is characterized by a pronounced adjuvant effect in irradiated animals.

  12. Local stem cell depletion model for normal tissue damage

    International Nuclear Information System (INIS)

    Yaes, R.J.; Keland, A.

    1987-01-01

    The hypothesis that radiation causes normal tissue damage by completely depleting local regions of tissue of viable stem cells leads to a simple mathematical model for such damage. In organs like skin and spinal cord where destruction of a small volume of tissue leads to a clinically apparent complication, the complication probability is expressed as a function of dose, volume and stem cell number by a simple triple negative exponential function analogous to the double exponential function of Munro and Gilbert for tumor control. The steep dose response curves for radiation myelitis that are obtained with our model are compared with the experimental data for radiation myelitis in laboratory rats. The model can be generalized to include other types or organs, high LET radiation, fractionated courses of radiation, and cases where an organ with a heterogeneous stem cell population receives an inhomogeneous dose of radiation. In principle it would thus be possible to determine the probability of tumor control and of damage to any organ within the radiation field if the dose distribution in three dimensional space within a patient is known

  13. On radiation damage to normal tissues and its treatment. Pt. 2

    International Nuclear Information System (INIS)

    Michalowski, A.S.

    1994-01-01

    In addition to transiently inhibiting cell cycle progression and sterilizing those cells capable of proliferation, irradiation disturbs the homeostasis effected by endogenous mediators of intercellular communication (humoral component of tissue response to radiation). Changes in the mediator levels may modulate radiation effects either by a assisting a return to normality (e.g., through a rise in H-type cell lineage-specific growth factors) or by aggravating the damage. The latter mode is illustrated with reports on changes in eicosanoid levels after irradiation and on results of empirical treatment of radiation injuries with anti-inflammatory drugs. Prodromal, acute and chronic effects of radiation are accompanied by excessive production of eicosanoids (prostaglandins, prostacyclin, thromboxanes and leukotrienes). These endogenous mediators of inflammatory reactions may be responsible for the vasodilatation, vasoconstriction, increased microvascular permeability, thrombosis and chemotaxis observed after radiation exposure. Glucocorticoids inhibit eicosanoid synthesis primarily by interfering with phospholipase A 2 whilst non-steroidal anti-inflammatory drugs prevent prostaglandin/thromboxane synthesis by inhibiting cycloxygenase. When administered after irradiation on empirical grounds, drugs belonging to both groups tend to attenuate a range of prodomal, acute and chronic effects of radiation in man and animals. Taken together, these two sets of observations are highly suggestive of a contribution of humoral factors to the adverse responses of normal tissues and organs to radiation. A full account of radiation damage should therefore consist of complementary descriptions of cellular and humoral events. Further studies on anti-inflammatory drug treatment of radiation damage to normal organs are justified and desirable. (orig.)

  14. On redistribution of alimentary vitamin E within irradiated rat tissues

    International Nuclear Information System (INIS)

    Paranich, A.V.; Chajkina, L.A.

    1992-01-01

    The data were presented concerning the content of lipopigments, vitamin E and malondialdehyde (MDA) in the brain and liver of rats. Excess vitamin E delivered with food was shown to be bound in tissues into complex with MDA. It was suggested that it was a labile form that reserves vitamin E. Irradiation of rats caused impairment of these complex and release of vitamin E, as well a decrease in the lipopigment fluorescence and increase in the MDA content

  15. Light ion irradiation for unfavorable soft tissue sarcoma

    International Nuclear Information System (INIS)

    Linstadt, D.; Castro, J.R.; Phillips, T.L.; Petti, P.L.; Collier, J.M.; Daftari, I.; Schoethaler, R.; Rayner, A.

    1990-09-01

    Between 1978 and 1989, 32 patients with unfavorable soft tissue sarcoma underwent light ion (helium, neon) irradiation with curative intent at Lawrence Berkeley Laboratory. The tumors were located in the trunk in 22 patients and head and neck in 10. Macroscopic tumor was present in 22 at the time of irradiation. Two patients had tumors apparently induced by previous therapeutic irradiation. Follow-up times for surviving patients ranged from 4 to 121 months (median 27 months). The overall 3-year actuarial local control rate was 62%; the corresponding survival rate was 50%. The 3-year actuarial control rate for patients irradiated with macroscopic tumors was 48%, while none of the patients with microscopic disease developed local recurrence (100%). The corresponding 3-year actuarial survival rates were 40% (macroscopic) and 78% (microscopic). Patients with retroperitoneal sarcoma did notably well; the local control rate and survival rate were 64% and 62%, respectively. Complications were acceptable; there were no radiation related deaths, while two patients (6%) required operations to correct significant radiation-related injuries. These results appear promising compared to those achieved by low -LET irradiation, and suggest that this technique merits further investigation

  16. Effects of Microwave Irradiation on Embryonic Brain Tissue.

    Science.gov (United States)

    1979-03-01

    less than 1 hour) post partum in the experiment described in Section III, page 13. Table 2 The significance of the difference in weight of the irradiated...appeared normal. Two of the control and two of the exposed rats showed small depressions of the external surface of the hemisphere unilaterally with...some thinning of the underlying cortex. The depressions occurred, one just dorsal to the rhinal fissure and the other lateral to the longitudinal sulcus

  17. Influence of low-energy laser radiation on normal skin and certain tumor tissues

    Energy Technology Data Exchange (ETDEWEB)

    Pletnev, S.D.; Karpenko, O.M.

    For some years, the authors' Institute has studied the influence of various types of low-energy laser radiation on normal tissue and the growth of tumors. Radiation at 3 and 30 J/cm/sup 2/ causes an increase in biological activity of various cell elements, manifested as an increase in mitotic activity of the cells in the basal layer of the epidermis, conglomeration of chromatin in the cell nuclei and an increase in degranulation of fat cells in the process of their migration to the reticular layer. Also noted was an increase in content of fibroblastic and lymphohistocytic elements in the dermis, as well as an increase in collagenization of connective tissue. It was found that irradiation of the skin by helium-neon, cadmium-helium and nitrogen lasers before and after grafting of the cells of various tumors modifies the course of the tumor process. This effect is apparently related to the fact that systematic irradiation results in changes creating a favorable background for survival and proliferation of tumor cells in the skin tissue medium. The changes facilitate an increase in survival and growth of both pigmented and nonpigmented tumors. Low power radiation stimulates the activity of the cells or cell structures; medium power stimulates their activity; high power suppresses activity.

  18. Radiation doses to normal tissues during craniospinal irradiation ...

    African Journals Online (AJOL)

    Mohamed Farouk Mostafa

    2011-10-15

    Oct 15, 2011 ... not in the center of the brain as this shows lower doses to eyes and lenses. ª 2011 Alexandria .... dose plan function was used to check the dose coverage of the .... maximum dose received by the right and left lens were listed.

  19. Radiation doses to normal tissues during craniospinal irradiation ...

    African Journals Online (AJOL)

    Objective: This dosimetric study is aiming to report the results of the analysis of doses received by target volumes and organs outside the target volumes during the treatment of medulloblastoma patients. And also by comparing the doses reaching the eyes and the lens with the use of different shielding methods.

  20. Statistical Validation of Normal Tissue Complication Probability Models

    Energy Technology Data Exchange (ETDEWEB)

    Xu Chengjian, E-mail: c.j.xu@umcg.nl [Department of Radiation Oncology, University of Groningen, University Medical Center Groningen, Groningen (Netherlands); Schaaf, Arjen van der; Veld, Aart A. van' t; Langendijk, Johannes A. [Department of Radiation Oncology, University of Groningen, University Medical Center Groningen, Groningen (Netherlands); Schilstra, Cornelis [Department of Radiation Oncology, University of Groningen, University Medical Center Groningen, Groningen (Netherlands); Radiotherapy Institute Friesland, Leeuwarden (Netherlands)

    2012-09-01

    Purpose: To investigate the applicability and value of double cross-validation and permutation tests as established statistical approaches in the validation of normal tissue complication probability (NTCP) models. Methods and Materials: A penalized regression method, LASSO (least absolute shrinkage and selection operator), was used to build NTCP models for xerostomia after radiation therapy treatment of head-and-neck cancer. Model assessment was based on the likelihood function and the area under the receiver operating characteristic curve. Results: Repeated double cross-validation showed the uncertainty and instability of the NTCP models and indicated that the statistical significance of model performance can be obtained by permutation testing. Conclusion: Repeated double cross-validation and permutation tests are recommended to validate NTCP models before clinical use.

  1. Statistical validation of normal tissue complication probability models.

    Science.gov (United States)

    Xu, Cheng-Jian; van der Schaaf, Arjen; Van't Veld, Aart A; Langendijk, Johannes A; Schilstra, Cornelis

    2012-09-01

    To investigate the applicability and value of double cross-validation and permutation tests as established statistical approaches in the validation of normal tissue complication probability (NTCP) models. A penalized regression method, LASSO (least absolute shrinkage and selection operator), was used to build NTCP models for xerostomia after radiation therapy treatment of head-and-neck cancer. Model assessment was based on the likelihood function and the area under the receiver operating characteristic curve. Repeated double cross-validation showed the uncertainty and instability of the NTCP models and indicated that the statistical significance of model performance can be obtained by permutation testing. Repeated double cross-validation and permutation tests are recommended to validate NTCP models before clinical use. Copyright © 2012 Elsevier Inc. All rights reserved.

  2. [FTIR study on the normal and cancerous stomach tissues].

    Science.gov (United States)

    Tong, Y; Lin, Y

    2001-06-01

    Tissues of cancerous and corresponding normal stomach were studied by FTIR technique. The results showed that there are obvious differences between FTIR spectra of them in spectral parameters such as frequency, intensity and band shape etc. The changes involving the phosphate symmetric stretching nu s, PO2- and asymmetric stretching nu as, PO2- modes, the CH3 and CH2 groups stretching (nu s, CH2, nu as, CH3) and bending (delta CH2) modes and the C-O stretching nu C-O mode were discussed. In addition, the changes of structure of hydrogen-bonding of nucleic acid and cell proteins and the packing and the conformational structure of the membrance lipids were analysed further. The average wavenumber of band of nu s, PO2- shifted from 1,080.92 cm-1 to 1,085.93 cm-1 and that of nu as, PO2- shifted from 1,239.64 cm-1 to 1,238.73 cm-1 which indicated that the degree of hydrogen-bonding formed by oxygen atom of the phosphodiester groups of nucleic acids was increased. The average wavenumber of band of delta CH2 of membrance lipids shifted from 1,455.23 cm-1 to 1,457.37 cm-1 that suggested that the conformational structure of the methylene chains of membrance lipids is more disordered than in normal tissues. The shift of band of nu C-O of cell proteins from 1,166.08 cm-1 to 1,166.58 cm-1 indicated that the hydrogen-bond of cell proteins become weaker.

  3. The claudin gene family: expression in normal and neoplastic tissues

    International Nuclear Information System (INIS)

    Hewitt, Kyle J; Agarwal, Rachana; Morin, Patrice J

    2006-01-01

    The claudin (CLDN) genes encode a family of proteins important in tight junction formation and function. Recently, it has become apparent that CLDN gene expression is frequently altered in several human cancers. However, the exact patterns of CLDN expression in various cancers is unknown, as only a limited number of CLDN genes have been investigated in a few tumors. We identified all the human CLDN genes from Genbank and we used the large public SAGE database to ascertain the gene expression of all 21 CLDN in 266 normal and neoplastic tissues. Using real-time RT-PCR, we also surveyed a subset of 13 CLDN genes in 24 normal and 24 neoplastic tissues. We show that claudins represent a family of highly related proteins, with claudin-16, and -23 being the most different from the others. From in silico analysis and RT-PCR data, we find that most claudin genes appear decreased in cancer, while CLDN3, CLDN4, and CLDN7 are elevated in several malignancies such as those originating from the pancreas, bladder, thyroid, fallopian tubes, ovary, stomach, colon, breast, uterus, and the prostate. Interestingly, CLDN5 is highly expressed in vascular endothelial cells, providing a possible target for antiangiogenic therapy. CLDN18 might represent a biomarker for gastric cancer. Our study confirms previously known CLDN gene expression patterns and identifies new ones, which may have applications in the detection, prognosis and therapy of several human cancers. In particular we identify several malignancies that express CLDN3 and CLDN4. These cancers may represent ideal candidates for a novel therapy being developed based on CPE, a toxin that specifically binds claudin-3 and claudin-4

  4. Salisphere derived c-Kit+ cell transplantation restores tissue homeostasis in irradiated salivary gland

    International Nuclear Information System (INIS)

    Nanduri, Lalitha S.Y.; Lombaert, Isabelle M.A.; Zwaag, Marianne van der; Faber, Hette; Brunsting, Jeanette F.; Os, Ronald P. van; Coppes, Robert P.

    2013-01-01

    Introduction: During radiotherapy salivary glands of head and neck cancer patients are unavoidably co-irradiated, potentially resulting in life-long impairment. Recently we showed that transplantation of salisphere-derived c-Kit expressing cells can functionally regenerate irradiated salivary glands. This study aims to select a more potent subpopulation of c-Kit + cells, co-expressing stem cell markers and to investigate whether long-term tissue homeostasis is restored after stem cell transplantation. Methods and results: Salisphere derived c-Kit + cells that co-expressed CD24 and/or CD49f markers, were intra-glandularly injected into 15 Gy irradiated submandibular glands of mice. Particularly, c-Kit + /CD24 + /CD49f + cell transplanted mice improved saliva production (54.59 ± 11.1%) versus the irradiated control group (21.5 ± 8.7%). Increase in expression of cells with differentiated duct cell markers like, cytokeratins (CK8, 18, 7 and 14) indicated functional recovery of this compartment. Moreover, ductal stem cell marker expression like c-Kit, CD133, CD24 and CD49f reappeared after transplantation indicating long-term functional maintenance potential of the gland. Furthermore, a normalization of vascularization as indicated by CD31 expression and reduction of fibrosis was observed, indicative of normalization of the microenvironment. Conclusions: Our results show that stem cell transplantation not only rescues hypo-salivation, but also restores tissue homeostasis of the irradiated gland, necessary for long-term maintenance of adult tissue

  5. Normal-tissue radioprotection by overexpression of the copper-zinc and manganese superoxide dismutase genes

    Energy Technology Data Exchange (ETDEWEB)

    Veldwijk, Marlon R. [Dept. of Radiation Oncology, Univ. Medical Center Mannheim, Univ. of Heidelberg, Mannheim (Germany); Pharmacology of Cancer Treatment (G402), German Cancer Research Center, Heidelberg (Germany); Herskind, Carsten; Wenz, Frederik [Dept. of Radiation Oncology, Univ. Medical Center Mannheim, Univ. of Heidelberg, Mannheim (Germany); Sellner, Leopold; Zeller, W. Jens [Pharmacology of Cancer Treatment (G402), German Cancer Research Center, Heidelberg (Germany); Radujkovic, Aleksandar [Dept. of Internal Medicine V, Univ. of Heidelberg (Germany); Laufs, Stephanie [Dept. of Experimental Surgery, Univ. Medical Center Mannheim, Univ. of Heidelberg, Mannheim (Germany); Molecular Oncology of Solid Tumors (G360), German Cancer Research Center, Heidelberg (Germany); Fruehauf, Stefan [Center for Tumor Diagnostic and Therapy, Paracelsus-Klinik, Osnabrueck (Germany)

    2009-08-15

    Background and Purpose: Protection of normal tissue against radiation-induced damage may increase the therapeutic ratio of radiotherapy. A promising strategy for testing this approach is gene therapy-mediated overexpression of the copper-zinc (CuZnSOD) or manganese superoxide dismutase (MnSOD) using recombinant adeno-associated viral (rAAV2) vectors. The purpose of this study was to test the modulating effects of the SOD genes on human primary lung fibroblasts (HPLF) after irradiation. Material and Methods: HPLF were transduced with rAAV2 vectors containing cDNA for the CuZnSOD, MnSOD or a control gene. The cells were irradiated (1-6 Gy), and gene transfer efficiency, apoptosis, protein expression/activity, and radiosensitivity measured by the colony-forming assay determined. Results: After transduction, 90.0% {+-} 6.4% of the cells expressed the transgene. A significant fivefold overexpression of both SOD was confirmed by an SOD activity assay (control: 21.1 {+-} 12.6, CuZnSOD: 95.1 {+-} 17.1, MnSOD: 108.5 {+-} 36.0 U SOD/mg protein) and immunohistochemistry. CuZnSOD and MnSOD overexpression resulted in a significant radioprotection of HPLF compared to controls (surviving fraction [SF] ratio SOD/control > 1): CuZnSOD: 1.18-fold (95% confidence interval [CI]: 1.06-1.32; p = 0.005), MnSOD: 1.23-fold (95% CI: 1.07-1.43; p = 0.01). Conclusion: Overexpression of CuZnSOD and MnSOD in HPLF mediated an increase in clonogenic survival after irradiation compared to controls. In previous works, a lack of radioprotection in SOD-overexpressing tumor cells was observed. Therefore, the present results suggest that rAAV2 vectors are promising tools for the delivery of radioprotective genes in normal tissue. (orig.)

  6. Histochemical differentiation between unirradiated and gamma-irradiated tissue in commercial use of some irradiated vegetables

    International Nuclear Information System (INIS)

    Foa, E.

    1978-01-01

    The use of gamma irradiation as a commercial method for the preservation of fruits and vegetables calls for methods of differentiation between unirradiated and irradiated products. A new approach to studying the influence of gamma irradiation on vegetable tissue at the cellular level by histochemical techniques has been developed by the authors and already applied to a number of fruits and vegetables. The possibility of evidencing radiation effects in the polysaccharide components of the cell wall suggested that these detected differences could be applied to differentiate irradiated from unirradiated tomatoes and potatoes. Some work done to determine changes in the cell wall polysaccharides of gamma-irradiated potatoes and tomatoes and to relate these changes to some other factors, such as storage time and vegetable variety, is reported here. While significant differences have been found in the optical densities of the total polysaccharides of the cell wall as a function of irradiation and of the other variables mentioned, it is not yet possible to use these values as a means of reliable differentiation. (author)

  7. Cell Proliferation during Lymphopoiesis in the Thymus of Normal and Continuously Irradiated Mice

    Energy Technology Data Exchange (ETDEWEB)

    Fabrikant, J. I. [Department of Radiological Science, Johns Hopkins University, Baltimore, MD (United States)

    1968-08-15

    The patterns of lymphoid cell proliferation in the thymus and spleen in normal and continuously irradiated young C57BL mice have been examined with techniques of flash and repeated labelling with tritiated thymidine and high resolution autoradiography. Changes in percentage labelling indices and labelled mitoses data have provided information on sites and rates of lymphoid cell proliferation in the thymus cortex (reticular cells, large, medium and small lymphocytes) and the spleen white pulp (germinal centre cells, large, medium and small lymphocytes). Labelling rates were fastest in the more primitive cell forms; in both lymphoid organs, the stem-cell labelling - reticular cells and germinal centre cells - reached 100% rapidly, whereas this was not the case for the different lymphocyte populations, and thymic lymphopoiesis was more rapid than splenic lymphopoiesis. Mean cycle times for thymus lymphoid cells were {approx} 12.5 hours for reticular cells, {approx} 9.5 hours for large lymphocytes, and {approx} 10.0 hours for medium and small lymphocytes; in the spleen, representative cycle times were significantly longer. Small lymphocytes were replaced at a greater rate in the thymus than in the spleen. Under continuous {gamma}-irradiation (caesium-137) at 45 rad/day and 75 rad/day for 15 days, there was a progressive depopulation of all lymphoid cell classes, an increase in the relative proportion of the more primitive forms, and a marked decrease in the numbers of small lymphocytes in both tissues. In the thymus and in the spleen, there was an increase in proliferation rates in both stem-cell populations and in all lymphoid cell forms, a decrease in mean cell cycle times to shorter values and a possible reduction in the spread of cell cycle times. In irradiated tissues, there was little evidence for lymphoid cell emigration. Tentative patterns of lymphopoiesis in the normal thymus and spleen based on the autoradiographic data aredescribed and changes in the

  8. Genomic instability: potential contributions to tumour and normal tissue response, and second tumours, after radiotherapy

    International Nuclear Information System (INIS)

    Hendry, Jolyon H.

    2001-01-01

    Purpose: Induced genomic instability generally refers to a type of damage which is transmissible down cell generations, and which results in a persistently enhanced frequency of de novo mutations, chromosomal abnormalities or lethality in a significant fraction of the descendant cell population. The potential contribution of induced genomic instability to tumour and normal tissue response, and second tumours, after radiotherapy, is explored. Results: The phenomenon of spontaneous genomic instability is well known in some rare genetic diseases (e.g. Gorlin's syndrome), and there is evidence in such cases that it can lead to a greater propensity for carcinogenesis (with shortened latency) which is enhanced after irradiation. It is unclear what role induced genomic instability plays in the response of normal individuals, but persistent chromosomal instability has been detected in vivo in lymphocytes and keratinocytes from irradiated normal individuals. Such induced genomic instability might play some role in tumour response in a subset of tumours with specific defects in damage response genes, but again its contribution to radiocurability in the majority of cancer patients is unclear. In normal tissues, genomic instability induced in wild-type cells leading to delayed cell death might contribute to more severe or prolonged early reactions as a consequence of increased cell loss, a longer time required for recovery, and greater residual injury. In tumours, induced genomic instability reflected in delayed reductions in clonogenic capacity might contribute to the radiosensitivity of primary tumours, and also to a lower incidence, longer latency and slower growth rate of recurrences and metastases. Conclusions: The evidence which is reviewed shows that there is little information at present to support these propositions, but what exists is consistent with their expectations. Also, it is not yet clear to what extent mutations associated with genomic instability

  9. Normal tissue tolerance to external beam radiation therapy: Ovaries

    International Nuclear Information System (INIS)

    Gross, E.; Champetier, C.; Zaccariotto, A.; Duberge, T.; Guerder, C.; Pointreau, Y.; Ortholan, C.; Chauvet, B.

    2010-01-01

    Clinical situations requiring protections of ovaries are mainly paediatric irradiations and pre-menopausal pelvic irradiations. The main complication of ovarian irradiation is the induced castration. Ovaries are extremely radiosensitive organs with strong interpersonal variations. The castrative effect of irradiation depends mainly on two factors: patient's age and the dose delivered to ovaries. The surgical technique of ovarian transposition allows to minimize the dose received by ovaries by taking them away, out of irradiation fields; the aim is to exclude them from the volume receiving 5 Gy or more, and if possible from those receiving 2 Gy. This technique becomes integrated into a multidisciplinary approach of conservation of fertility for patients exposed to other cytotoxic treatments. (authors)

  10. Cell Survival and DNA Damage in Normal Prostate Cells Irradiated Out-of-Field.

    LENUS (Irish Health Repository)

    Shields, L

    2014-10-31

    Interest in out-of-field radiation dose has been increasing with the introduction of new techniques, such as volumetric modulated arc therapy (VMAT). These new techniques offer superior conformity of high-dose regions to the target compared to conventional techniques, however more normal tissue is exposed to low-dose radiation with VMAT. There is a potential increase in radiobiological effectiveness associated with lower energy photons delivered during VMAT as normal cells are exposed to a temporal change in incident photon energy spectrum. During VMAT deliveries, normal cells can be exposed to the primary radiation beam, as well as to transmission and scatter radiation. The impact of low-dose radiation, radiation-induced bystander effect and change in energy spectrum on normal cells are not well understood. The current study examined cell survival and DNA damage in normal prostate cells after exposure to out-of-field radiation both with and without the transfer of bystander factors. The effect of a change in energy spectrum out-of-field compared to in-field was also investigated. Prostate cancer (LNCaP) and normal prostate (PNT1A) cells were placed in-field and out-of-field, respectively, with the PNT1A cells being located 1 cm from the field edge when in-field cells were being irradiated with 2 Gy. Clonogenic and γ-H2AX assays were performed postirradiation to examine cell survival and DNA damage. The assays were repeated when bystander factors from the LNCaP cells were transferred to the PNT1A cells and also when the PNT1A cells were irradiated in-field to a different energy spectrum. An average out-of-field dose of 10.8 ± 4.2 cGy produced a significant reduction in colony volume and increase in the number of γ-H2AX foci\\/cell in the PNT1A cells compared to the sham-irradiated control cells. An adaptive response was observed in the PNT1A cells having first received a low out-of-field dose and then the bystander factors. The PNT1A cells showed a significant

  11. Radiobiological predictors of tumor and acute normal tissue response in radiotherapy for head and neck cancers

    International Nuclear Information System (INIS)

    Maciejewski, B.; Skladowski, K.; Zajusz, A.

    1991-01-01

    The importance of measurements of the potential doubling time (T pot. ) and of the survival fraction at 2.0 Gy (SF 2 ), and a method modifying acute radiation response of normal oral mucosa are discussed. Tumor clonogen repopulation accelerates around day 28 of the treatment, and the rate of repopulation is not constant but continuously increases from about 0.3 Gy/day to 1.0-1.3 Gy/day between day 28 and 65 of the treatment. This may suggest that T pot. values decrease correspondingly. The relevance of prior-to-treatment T pot. measurements to clinical situations is discussed. The SF 2 value reflects the intrinsic radiosensitivity of human tumors. The SF 2 values are expected to be valuable as predictors for tumor response to irradiation. Variations in the SF 2 values depending on tumor characteristics and assay methods are discussed in relation to the dose response and tumor cure probability. The effect of modifying the repopulation rate in the oral mucosa by stimulation with a 2% silver nitrate solution is discussed. Although these prognosticators are different in their nature, they might provide a rational basis for selecting patients into optimal irradiation treatment and might allow to modify the radiation response of dose-limiting normal tissues. (author). 5 figs., 1 tab., 28 refs

  12. Radiation therapy and late reactions in normal tissues

    International Nuclear Information System (INIS)

    Aoyama, Takashi; Kuroda, Yasumasa

    1998-01-01

    Recent developments in cancer therapy have made us increasingly aware that the quality of life of a patient is as valuable as other benefits received from therapy. This awareness leads to an emphasis on organ and/or function preservation in the course of therapy. In line with this new thinking, greater consideration is placed on radiation therapy as an appropriate modality of cancer therapy. Possible complications in normal tissues, especially those of late reaction type after the therapy must be overcome. This review, therefore, focuses on recent progress of studies on mechanisms of the complications of the late reaction type. An observation of a clinical case concerning a late reaction of spinal cord (radiation myelopathy) and surveys of experimental studies on the mechanisms of late reactions (including radiation pneumonitis and lung fibrosis, and radiation response of vascular endothelial cells) provide a hypothesis that apoptosis through the pathway starting with radiation-induced sphingomyelin hydrolysis may play an important role in causing a variety of late reactions. This insight is based on the fact that radiation also activates protein kinase C which appears to block apoptosis. The mechanisms of late reactions, therefore, may involve a balance between radiation-induced apoptotic death and its down regulation by suppressor mechanisms through protein kinase C. (author)

  13. Acute and late effects of multimodal therapy on normal tissues

    International Nuclear Information System (INIS)

    Phillips, T.L.; Fu, K.K.

    1977-01-01

    The increasing use of combined radiation, chemotherapy, and surgery has led to an increased incidence of acute and late complications. The complications are, in general, similar to those seen with each modality alone, but occur with increased incidence. Enhanced effects of combined radiation and surgery are modest in number and consist primarily of problems with wound healing and fibrosis, as well as late gastrointestinal damage. Combinations of radiotherapy and chemotherapy have shown a greater degree of enhanced acute and late reactions. Drugs, such as actinomycin-D and Adriamycin, are particularly dangerous if the marked enhancement of radiation effects caused by the drugs in almost all organs is not appreciated and the radiation dose not adjusted accordingly. Proper selection of drugs can lead to enhanced local control by radiotherapy and/or surgery, as well as eradication of microscopic distant metastases, without increased normal tissue injury. Late induction of malignancy can occur with either radiation or chemotherapy alone and, in some cases, this appears to be enhanced when they are combined

  14. Screening of the residual normal ovarian tissue adjacent to orthotopic epithelial ovarian carcinomas in nude mice.

    Science.gov (United States)

    Zhu, G H; Wang, S T; Yao, M Z; Cai, J H; Chen, C Y; Yang, Z X; Hong, L; Yang, S Y

    2014-04-16

    The objective of this study was to explore the feasibility and methods of screening the residual normal ovarian tissue adjacent to orthotopic ovarian carcinomas in nude mice. Human epithelial ovarian cancer cells (OVCAR3) were subcutaneously implanted for a tumor source and ovarian orthotopic transplantation. The cancer tissue, proximal paraneoplastic tissue, middle paraneoplastic tissue, remote paraneoplastic tissue, and normal ovarian tissue were removed. CK-7, CA125, p53, survivin, MMP-2, and TIMP-2 expression was detected by reverse transcription polymerase chain reaction. We obtained 35 paraneoplastic residual ovarian tissues with normal biopsies from 40 cases of an orthotopic epithelial ovarian carcinoma model (87.5%). CK-7, CA125, p53, survivin, MMP-2, and TIMP-2 expression was lower in proximal paraneoplastic tissue than in cancer tissue (P tissue (P tissue as well as among residual normal ovarian tissues with different severity (P > 0.05). In ovarian tissues of 20 normal nude mice, the expression of CK- 7, CA125, p53, survivin, MMP-2, and TIMP-2 was negative. Overall, the expression levels of CK-7, CA125, p53, survivin, MMP-2, TIMP-2, and other molecular markers showed a decreasing trend in the non-cancer tissue direction. The expression levels can be used as standards to screen residual normal ovarian tissue. We can obtain relatively safe normal ovarian tissues adjacent to epithelial ovarian cancer.

  15. Correlation of in vitro lymphocyte radiosensitivity and gene expression with late normal tissue reactions following curative radiotherapy for breast cancer

    International Nuclear Information System (INIS)

    Finnon, Paul; Kabacik, Sylwia; MacKay, Alan; Raffy, Claudine; A’Hern, Roger; Owen, Roger; Badie, Christophe; Yarnold, John; Bouffler, Simon

    2012-01-01

    Background and purpose: Identification of mechanisms of late normal tissue responses to curative radiotherapy that discriminate individuals with marked or mild responses would aid response prediction. This study aimed to identify differences in gene expression, apoptosis, residual DNA double strand breaks and chromosomal damage after in vitro irradiation of lymphocytes in a series of patients with marked (31 cases) or mild (28 controls) late adverse reaction to adjuvant breast radiotherapy. Materials and methods: Gene expression arrays, residual γH2AX, apoptosis, G2 chromosomal radiosensitivity and G0 micronucleus assay were used to compare case and control lymphocyte radiation responses. Results: Five hundred and thirty genes were up-regulated and 819 down-regulated by ionising radiation. Irradiated samples were identified with an overall cross-validated error rate of 3.4%. Prediction analyses to classify cases and controls using unirradiated (0 Gy), irradiated (4 Gy) or radiation response (4–0 Gy) expression profiles correctly identified samples with, respectively, 25%, 22% or 18.5% error rates. Significant inter-sample variation was observed for all cellular endpoints but cases and controls could not be distinguished. Conclusions: Variation in lymphocyte radiosensitivity does not necessarily correlate with normal tissue response to radiotherapy. Gene expression analysis can predict of radiation exposure and may in the future help prediction of normal tissue radiosensitivity.

  16. Responses of vibrissa-sensitive cortical neurons in normal and prenatally x-irradiated rat

    International Nuclear Information System (INIS)

    Ito, M.; Kawabata, M.; Shoji, R.

    1979-01-01

    Rats were irradiated by 200 R of x ray on day 17 of gestation through the body wall of the mother. When they underwent the following electrophysiological tests at the age of 3 to 4 month, the somatosensory cortex showed a lack of layers II, III, IV, and Va. Spike responses to quick whisker deflections were recorded from single cells in the somatosenory cortex of normal and prenatally x-irradiated rats. For the irradiated rats the response latency was prolonged when compared to the normal controls. Cortical laminar analysis of field potentials revealed that there was no difference in the latency of these potentials between the two groups, suggesting that vibrissal sensory signals reach the cortical level normally even in the irradiated rats. The prolonged latency of the irradiated cortical neuronal response could thus be ascribed to an abnormal intracortical delay, which was most likely associated with the failure of development of layer IV stellate cells in these preparations

  17. The effects of normal paraffins mobilizers on irradiated polypropylene

    International Nuclear Information System (INIS)

    Chen Wenxiu; Gao Ling

    1995-01-01

    The n-paraffins blended with polypropylene (PP) as mobilizer had been investigated. The effectiveness of mobilizer (n-paraffins) on irradiated polypropylene is dependent on the molecular weight of mobilizer and its content on polypropylene. The n-docosame (n-C 22 ) possesses the best effectiveness of radiation tolerance on PP among the mobilizer paraffins: n-decane (n-C 10 ), n-hexadecane (n-C 16 ), n-docosane (n-C 22 ) and n-hexatriacontane (n-C 36 ). The 2% (w/w) content of a given mobilizer is the most effective at reducing the embrittlement of irradiated PP as evidenced by the elongation at break. The physical properties of polypropylene with mobilizers such as density, Young's modulus, the Fraction of free volume and the weight swelling ratio in p-xylene at room temperature were measured. Above phenomena are related with the constructive of blended PP and demonstrated by its physical properties

  18. Radiation damage to the normal monkey brain. Experimental study induced by interstitial irradiation

    International Nuclear Information System (INIS)

    Mishima, Nobuya; Tamiya, Takashi; Matsumoto, Kengo; Furuta, Tomohisa; Ohmoto, Takashi

    2003-01-01

    Radiation damage to normal brain tissue induced by interstitial irradiation with iridium-192 seeds was sequentially evaluated by computed tomography (CT), magnetic resonance imaging (MRI), and histological examination. This study was carried out in 14 mature Japanese monkeys. The experimental area received more than 200-260 Gy of irradiation developed coagulative necrosis. Infiltration of macrophages to the periphery of the necrotic area was seen. In addition, neovascularization, hyalinization of vascular walls, and gliosis were found in the periphery of the area invaded by the macrophages. All sites at which the vascular walls were found to have acute stage fibrinoid necrosis eventually developed coagulative necrosis. The focus of necrosis was detected by MRI starting 1 week after the end of radiation treatment, and the size of the necrotic area did not change for 6 months. The peripheral areas showed clear ring enhancement with contrast material. Edema surrounding the lesions was the most significant 1 week after radiation and was reduced to a minimum level 1 month later. However, the edema then expanded once again and was sustained for as long as 6 months. CT did not provide as clear of a presentation as MRI, but it did reveal similar findings for the most part, and depicted calcification in the necrotic area. This experimental model is considered useful for conducting basic research on brachytherapy, as well as for achieving a better understanding of delayed radiation necrosis. (author)

  19. Calculation of normal tissue complication probability and dose-volume histogram reduction schemes for tissues with a critical element architecture

    International Nuclear Information System (INIS)

    Niemierko, Andrzej; Goitein, Michael

    1991-01-01

    The authors investigate a model of normal tissue complication probability for tissues that may be represented by a critical element architecture. They derive formulas for complication probability that apply to both a partial volume irradiation and to an arbitrary inhomogeneous dose distribution. The dose-volume isoeffect relationship which is a consequence of a critical element architecture is discussed and compared to the empirical power law relationship. A dose-volume histogram reduction scheme for a 'pure' critical element model is derived. In addition, a point-based algorithm which does not require precomputation of a dose-volume histogram is derived. The existing published dose-volume histogram reduction algorithms are analyzed. The authors show that the existing algorithms, developed empirically without an explicit biophysical model, have a close relationship to the critical element model at low levels of complication probability. However, it is also showed that they have aspects which are not compatible with a critical element model and the authors propose a modification to one of them to circumvent its restriction to low complication probabilities. (author). 26 refs.; 7 figs

  20. Proteolytic processing of connective tissue growth factor in normal ocular tissues and during corneal wound healing.

    Science.gov (United States)

    Robinson, Paulette M; Smith, Tyler S; Patel, Dilan; Dave, Meera; Lewin, Alfred S; Pi, Liya; Scott, Edward W; Tuli, Sonal S; Schultz, Gregory S

    2012-12-13

    Connective tissue growth factor (CTGF) is a fibrogenic cytokine that is up-regulated by TGF-β and mediates most key fibrotic actions of TGF-β, including stimulation of synthesis of extracellular matrix and differentiation of fibroblasts into myofibroblasts. This study addresses the role of proteolytic processing of CTGF in human corneal fibroblasts (HCF) stimulated with TGF-β, normal ocular tissues and wounded corneas. Proteolytic processing of CTGF in HCF cultures, normal animal eyes, and excimer laser wounded rat corneas were examined by Western blot. The identity of a 21-kDa band was determined by tandem mass spectrometry, and possible alternative splice variants of CTGF were assessed by 5' Rapid Amplification of cDNA Ends (RACE). HCF stimulated by TGF-β contained full length 38-kDa CTGF and fragments of 25, 21, 18, and 13 kDa, while conditioned medium contained full length 38- and a 21-kDa fragment of CTGF that contained the middle "hinge" region of CTGF. Fragmentation of recombinant CTGF incubated in HCF extracts was blocked by the aspartate protease inhibitor, pepstatin. Normal mouse, rat, and rabbit whole eyes and rabbit ocular tissues contained abundant amounts of C-terminal 25- and 21-kDa fragments and trace amounts of 38-kDa CTGF, although no alternative transcripts were detected. All forms of CTGF (38, 25, and 21 kDa) were detected during healing of excimer ablated rat corneas, peaking on day 11. Proteolytic processing of 38-kDa CTGF occurs during corneal wound healing, which may have important implications in regulation of corneal scar formation.

  1. Elemental composition of 'normal' and Alzheimer brain tissue by INA and PIXE analyses

    International Nuclear Information System (INIS)

    Stedman, J.D.; Spyrou, N.M.

    1997-01-01

    Instrumental methods based on the nuclear and atomic properties of the elements have been used for many years to determine elemental concentrations in a variety of materials for biomedical, industrial and environmental applications. These methods offer high sensitivity for accurate trace element measurements, suffer few interfering or competing effects. Present no blank problems and are convenient for both research and routine analyses. The present article describes the use of two trace element techniques. Firstly the use of activation of stable nuclei irradiated by neutrons in the core of a low power research reactor as a means of detection of elements through the resulting gamma-rays emitted. Secondly, the observations of the interactions of energetic ion beams with the material in order to identify elemental species. Over recent years there has been some interest in determining the elemental composition of 'normal' and Alzheimer affected brain tissue, however literature findings are inconsistent. Possible reasons for discrepancies need to be identified for further progress to be made. Here, post-mortem tissue samples, provided by the Alzheimer's Disease Brain Bank, Institute of Psychiatry, London, were taken from the frontal, occipital, parietal and temporal lobes of both hemispheres of brains from 13 'normal' and 19 Alzheimer subjects. The elemental composition of the samples was determined using the analytical techniques of INAA (instrumental neutron activation analysis), RBS (Rutherford back-scattering) and PIXE (particle induced x-ray emission). The principal findings are summarised here. (author)

  2. Normal Tissue Complication Probability Modeling of Acute Hematologic Toxicity in Cervical Cancer Patients Treated With Chemoradiotherapy

    International Nuclear Information System (INIS)

    Rose, Brent S.; Aydogan, Bulent; Liang, Yun; Yeginer, Mete; Hasselle, Michael D.; Dandekar, Virag; Bafana, Rounak; Yashar, Catheryn M.; Mundt, Arno J.; Roeske, John C.; Mell, Loren K.

    2011-01-01

    Purpose: To test the hypothesis that increased pelvic bone marrow (BM) irradiation is associated with increased hematologic toxicity (HT) in cervical cancer patients undergoing chemoradiotherapy and to develop a normal tissue complication probability (NTCP) model for HT. Methods and Materials: We tested associations between hematologic nadirs during chemoradiotherapy and the volume of BM receiving ≥10 and 20 Gy (V 10 and V 20 ) using a previously developed linear regression model. The validation cohort consisted of 44 cervical cancer patients treated with concurrent cisplatin and pelvic radiotherapy. Subsequently, these data were pooled with data from 37 identically treated patients from a previous study, forming a cohort of 81 patients for normal tissue complication probability analysis. Generalized linear modeling was used to test associations between hematologic nadirs and dosimetric parameters, adjusting for body mass index. Receiver operating characteristic curves were used to derive optimal dosimetric planning constraints. Results: In the validation cohort, significant negative correlations were observed between white blood cell count nadir and V 10 (regression coefficient (β) = -0.060, p = 0.009) and V 20 (β = -0.044, p = 0.010). In the combined cohort, the (adjusted) β estimates for log (white blood cell) vs. V 10 and V 20 were as follows: -0.022 (p = 0.025) and -0.021 (p = 0.002), respectively. Patients with V 10 ≥ 95% were more likely to experience Grade ≥3 leukopenia (68.8% vs. 24.6%, p 20 > 76% (57.7% vs. 21.8%, p = 0.001). Conclusions: These findings support the hypothesis that HT increases with increasing pelvic BM volume irradiated. Efforts to maintain V 10 20 < 76% may reduce HT.

  3. THE PRESENCE OF ENDOGENOUS PYROGEN IN NORMAL RABBIT TISSUES.

    Science.gov (United States)

    SNELL, E S; ATKINS, E

    1965-06-01

    Saline extracts of homogenized, uninfected, rabbit tissues produced febrile responses when injected intravenously into rabbits. Extracts of muscle, lung, and heart evoked fevers that were similar to those induced by leucocyte pyrogen; extracts of spleen, liver, and kidney caused more sustained fevers. The minimal pyrogenic dose appeared to be between 1.5 and 3 gm wet weight of tissue. Evidence is presented that neither Gram-negative bacterial endotoxin nor polymorphonuclear leucocytes (circulating or sequestered in the tissues) can be implicated as the source of pyrogen in tissue extracts. It seems likely, therefore, that a pyrogenic material of truly endogenous origin is widely distributed in tissues. Tissue pyrogen appears to be a large molecule which is relatively resistant to treatment with acid but not with alkali. Possible pathological roles for this endogenous agent (or agents) are briefly indicated.

  4. Dose effect comparisons between HFR and BMRR irradiated dogs with respect to healthy tissue tolerance

    International Nuclear Information System (INIS)

    Huiskamp, R.; Philipp, K.H.I.; Gavin, P.R.; Wheeler, F.J.; Siefert, A.

    1993-01-01

    Epithermal neutron beams are being developed for the application of boron neutron capture therapy (BNCT) of deep seated tumors, like glioblastoma and astrocytomas, through the intact skin. Epithermal neutrons will be moderated by the tissue mass between skin and tumour to produce the thermal neutrons necessary for the 10 B(n,α) 7 Li reaction in the target tissue. Although the neutron capture cross-sections of elements in normal tissue are several orders of magnitude lower that for boron, the high abundance of hydrogen and nitrogen will cause a significant contribution to the total absorbed radiation dose through the 1 H(n,γ) 2 H and the 14 N(n,p) 14 C reaction, respectively. Due to inevitable incomplete filtration, an epithermal beam will also contain a fast neutron component, i.e. neutrons with energies ≥ 10 keV, and a γ-photon component originating from the reactor and produced in structural and filter materials. Therefore, the resultant radiation consists of a complex of low and high LET radiation of which the constitutents vary rapidly with depth in tissue. Based on the ongoing canine healthy tissue tolerance study at the Brookhaven Medical Research Reactor (BMRR) using the epithermal beam without BSH, the relative biological effectiveness (RBE) of the fast neutron beam component has been determined for skin reactions. In addition, a open-quotes compound factorclose quotes, i.e geometry x RBE, for the 10 B(n,α) 7 Li reaction was derived for dogs irradiated at the BMRR with the epithermal beam and BSH (Gavin et al.). Currently, a healthy tissue tolerance study with BSH is being carried out at the HB11 epithermal beam of the High Flux Reactor at Petten. The present paper describes preliminary dose effect comparisons between High Flux Reactor (HFR) and BMRR irradiated dogs with respect to healthy tissue tolerance in order to refine the BSH compound factors and the fast neutron RBE for skin and brain

  5. Combined effects of radiotherapy and chemotherapy normal tissue, 1

    International Nuclear Information System (INIS)

    Watanabe, Noriaki

    1983-01-01

    The combined effects of radiation and drugs on the fine vasculature of mouse liver were investigated by microangiography. The fine vasculature of the liver showed dilatations one day after 1000 rad of irradiation to the liver. The fine vasculature of the liver showed marked dilatations and slight extravasations one day after 1000 rad of irradiation to the whole body. The fine vasculature of the liver showed dilatations and partial narrowings after the administration of BLM, 2mg/kg/day ip for 5 days. The combined effects of BLM and radiation was greater than that with radiation alone. The fine vasculature of the liver showed marked dilatations and slight extravasation after the administration of BLM, 2mg/kg/day ip for 5 days and MMC 2mg/kg ip on day 6. This findings is about the same as that after the administration of BLM and 1000 rad of irradiation. The administration of urokinase did not diminish the effects of radiation on the fine vasculature of the liver. The administration of YM-08310 diminished the effects of irradiation on the fine vasculature of the liver. (author)

  6. Activity of pyrimidine degradation enzymes in normal tissues

    NARCIS (Netherlands)

    van Kuilenburg, A. B. P.; van Lenthe, H.; van Gennip, A. H.

    2006-01-01

    In this study, we measured the activity of dihydropyrimidine dehydrogenase (DPD), dihydropyrimidinase (DHP) and beta-ureidopropionase (beta-UP), using radiolabeled substrates, in 16 different tissues obtained at autopsy from a single patient. The activity of DPD could be detected in all tissues

  7. Tissue breathing and topology of rats thymocytes surface under acute total γ-irradiation.

    Science.gov (United States)

    Nikitina, I A; Gritsuk, A I

    2017-12-01

    Assessment of the effect of single total γ irradiation to the parameters of mitochondrial oxidation and the topology of the thymocyte surface. The study was performed in sexually mature white outbreeding male rats divided into three groups: two experimental and one control. The states of energy metabolism were determined by the rate of oxygen consumption by the thymus tissues on endogenous substrates at the presence of 2,4 dinitrophenol, uncoupler of a tissue breathing (TB) and oxidative phosphorylation (OP) after a single total γ irradiation at a dose of 1.0 Gy at 3, 10, 40 and 60 days. The topology of thymus cells was assessed using atomic force microscopy (AFM) and scanning electron microscopy (SEM). On the 3rd and 10th days after total gamma irradiation at a dose of 1.0 Gy, a significant decrease in respira tory activity was determined in thymus tissues on endogenous substrates. Simultaneously, on the 3rd day, pro nounced changes in the morphological parameters of thymocytes (height, volume, area of contact with the sub strate) and the topology of their surface were also observed. On the 10th day after irradiation, most of the morpho logical parameters of thymocytes, except for their volume, were characterized by restoration to normal. In the long term (on the 30th and 60th days after exposure), a gradual but not complete recovery of the respiratory activity of thymocytes was observed, accompanied by an increase in the degree of dissociation of TD and OP. The obtained data reflect and refine mechanisms of post radiation repair of lymphopoiesis, showing the presence of conjugated changes in the parameters of aerobic energy metabolism of thymocytes, morphology and topology of their surface. The synchronism of changes in the parameters under study is a reflection of the state of the cytoskeleton, the functional activity of which largely depends on the level and efficiency of mitochondrial oxidation. І. A. Nikitina, A. I. Gritsuk.

  8. On the participation of irradiated tissues in the formation of limb regenerate in axolotls

    International Nuclear Information System (INIS)

    Tuchkova, S.Ya.

    1976-01-01

    The aim of the study was to obtain further information on the participation of irradiated tissue cells in formation of regenerated limbs after X-irradiation of axolotls and experimental restoration of the regenerational ability. Cells of irradiated tissues were labeled with H 3 -thymidine; the presence of the label in regenerated tissues would be indicative of participation of irradiated cells in the regeneration process. Irradiation dose was 700 R. 30 axolotls with irradiated limbs were intramuscularly injected with rat muscle homogenate into the right limb once a day beginning from the day of treatment. 15 similarly irradiated animals which did not receive homogenate served as a control. The authors concluded that the presence of highly labeled cells in regenerated tissues was likely to indicate the participation of irradiated tissue cells in regeneration of the limb. However, the quantitative contribution of such cells was impossible to determine since remaining irradiated tissues of the organ contained mostly unlabeled cells. It was also impossible to rule out the possibility of cell migration from non-irradiated tissues [ru

  9. Human fibroblast strain with normal survival but abnormal postreplication repair after ultraviolet light irradiation

    International Nuclear Information System (INIS)

    Doniger, J.; Barrett, S.F.; Robbins, J.H.

    1980-01-01

    Postreplication repair has been studied in ultraviolet light (UV-irradiated) fibroblast strains derived from eight apparently normal control donors and seven xeroderma pigmentosum patients. One control donor strain had an intermediate defect in postreplication repair similar to that in excision-deficient xeroderma pigmentosum fibroblasts. However, unlike the xeroderma pigmentosum strains, this control donor strain had normal UV-induced unscheduled DNA synthesis and normal survival after irradiation with UV. This unique fibroblast strain should be useful in studies designed to elucidate the possible role of postreplication repair in UV-induced carcinogenesis and mutagenesis

  10. Cell survival of human tumor cells compared with normal fibroblasts following 60Co gamma irradiation

    International Nuclear Information System (INIS)

    Lloyd, E.L.; Henning, C.B.; Reynolds, S.D.; Holmblad, G.L.; Trier, J.E.

    1982-01-01

    Three tumor cell lines, two of which were shown to be HeLa cells, were irradiated with 60 Co gamma irradiation, together with two cell cultures of normal human diploid fibroblasts. Cell survival was studied in three different experiments over a dose range of 2 to 14 gray. All the tumor cell lines showed a very wide shoulder in the dose response curves in contrast to the extremely narrow shoulder of the normal fibroblasts. In addition, the D/sub o/ values for the tumor cell lines were somewhat greater. These two characteristics of the dose response curves resulted in up to 2 orders of magnitude less sensitivity for cell inactivation of HeLa cells when compared with normal cells at high doses (10 gray). Because of these large differences, the extrapolation of results from the irradiation of HeLa cells concerning the mechanisms of normal cell killing should be interpreted with great caution

  11. Normal morphogenesis of epithelial tissues and progression of epithelial tumors

    Science.gov (United States)

    Wang, Chun-Chao; Jamal, Leen; Janes, Kevin A.

    2011-01-01

    Epithelial cells organize into various tissue architectures that largely maintain their structure throughout the life of an organism. For decades, the morphogenesis of epithelial tissues has fascinated scientists at the interface of cell, developmental, and molecular biology. Systems biology offers ways to combine knowledge from these disciplines by building integrative models that are quantitative and predictive. Can such models be useful for gaining a deeper understanding of epithelial morphogenesis? Here, we take inventory of some recurring themes in epithelial morphogenesis that systems approaches could strive to capture. Predictive understanding of morphogenesis at the systems level would prove especially valuable for diseases such as cancer, where epithelial tissue architecture is profoundly disrupted. PMID:21898857

  12. Irradiation-induced hypoxia in bones and soft tissues: an experimental study

    International Nuclear Information System (INIS)

    Aitasalo, K.; Aro, H.

    1986-01-01

    Bone marrow and subcutaneous tissue pO 2 and pCO 2 were measured by means of implanted tissue tonometers in irradiated and nonirradiated rabbit hind limbs. The x-ray dose was 500, 1000, 1500, 2000, and 3000 rads. Tissue gas tensions were measured 1 day and 5 and 11 weeks after radiation. The pCO 2 changes in both tissues were slight but not statistically significant. The subcutaneous tissue pO 2 decreased during the acute phase of irradiation injury, and the effect of irradiation was dose-dependent. Later on, irradiation had no significant effects on the subcutaneous pO 2 , although light microscopy of the affected tissues showed fibrosis and blood vessel changes. The response of the subcutaneous pO 2 to systemic hyperoxia also increased in the chronic phase of irradiation injury as a sign of improved microcirculation. The bone marrow showed a high radiosensitivity. Irradiation caused a rapid dose-dependent decrease of the marrow pO 2 , and the marrow pO 2 decreased with time during the chronic phase of irradiation injury. The marrow pO 2 responded slowly and marginally to an increment of arterial pO 2 during breathing 100% oxygen as further evidence of impaired vascular pattern. The results showed that irradiation causes only a transient impairment of tissue perfusion in the skin. However, irradiation-damaged marrow was characterized by progressive tissue hypoxia

  13. Trace element load in cancer and normal lung tissue

    International Nuclear Information System (INIS)

    Kubala-Kukus, A.; Braziewicz, J.; Banas, D.; Majewska, U.; Gozdz, S.; Urbaniak, A.

    1999-01-01

    Samples of malignant and benign human lung tissues were analysed by two complementary methods, i.e., particle induced X-ray emission (PIXE) and total reflection X-ray fluorescence (TRXRF). The concentration of trace elements of P, S, K, Ca, Ti, Cr, Mn, Fe, Cu, Zn, Se, Sr, Hg and Pb was determined in squamous cancer of lung tissue from 65 people and in the benign lung tumour tissue from 5 people. Several elements shows enhancement in cancerous lung tissue of women in comparison to men, i.e., titanium show maximum enhancement by 48% followed by Cr (20%) and Mn (36%). At the same time trace element concentration of Sr and Pb are declaimed by 30% and 20% in women population. Physical basis of used analytical methods, experimental set-up and the procedure of sample preparation are described

  14. Tolerance of normal tissues to radiation therapy: Ear

    International Nuclear Information System (INIS)

    Fleury, B.; Lapeyre, M.

    2010-01-01

    The main objective of this work was to describe, based on a literature survey, the radiation-induced toxicity of the ear and to try to establish the limiting dose. The limiting toxicity was the sensorineural hearing loss. A dose-effect relationship has been described by several authors. Thirty to 40% of patients who are irradiated for head and neck cancer are concerned, but the intensity of the hearing loss tends to depend on the exact localisation of the primary tumour: nasopharyngeal irradiations, paranasal sinusal and parotid irradiation are at greater risk of complication. High frequencies are more vulnerable than the lower ones. Age of patients, as well as baseline hearing abilities, deeply influence the issue. As far as possible, the dose to the inner ear (the cochlea more precisely) should be kept under 40 Gy. In case of association with other causes of toxicity (such as age, low baseline value, association to cisplatin), this dose should be as low as possible. Should carcinologic constraints lead to toxic doses, then patients should be properly informed. (authors)

  15. Feasibility of temporary protective embolization of normal liver tissue using degradable starch microspheres during radioembolization of liver tumours

    International Nuclear Information System (INIS)

    Meyer, Carsten; Pieper, Claus Christian; Wilhelm, Kai E.; Schild, Hans Heinz; Ezziddin, Samer; Ahmadzadehfar, Hojjat

    2014-01-01

    To describe a new approach to protect nontarget healthy liver tissue using degradable starch microspheres (DSM) as a short-term embolizate during radioembolization of liver tumours with 90 Y microspheres. Between December 2011 and July 2012 radioembolization was performed in 54 patients. Five of these patients (three women, two men; mean age 67 years) underwent protective temporary embolization using DSM (EmboCept registered S) of normal liver tissue that could not be excluded from the area treated by radioembolization through catheter repositioning. Clinical symptoms, laboratory findings, preinterventional imaging, and 99m Tc-MAA and bremsstrahlung SPECT/CT, as well as baseline and follow-up imaging with 18 F-FDG PET/CT and MRI, were evaluated in relation to the technical and clinical success of the protective embolization. Temporary embolization of arteries supplying normal liver tissue using DSM was technically successful in all five patients. 99m Tc-MAA SPECT/CT performed in the first two patients after DSM injection showed no increased pulmonary shunting compared to the MAA test injection without DSM. Bremsstrahlung SPECT/CT after radioembolization demonstrated satisfactory irradiation of the tumour and successful protection of normal liver tissue. There were only mild hepatotoxic effects (grade 1) on laboratory follow-up examinations, and no adverse events associated with DSM embolization or radioembolization were recorded. Temporary embolization with DSM before radioembolization is feasible and can effectively protect areas of normal liver tissue from irradiation and avoid permanent embolization if other methods such as catheter repositioning are not possible due to the location of the metastases. (orig.)

  16. Feasibility of temporary protective embolization of normal liver tissue using degradable starch microspheres during radioembolization of liver tumours

    Energy Technology Data Exchange (ETDEWEB)

    Meyer, Carsten [University of Bonn, Department of Radiology, Bonn (Germany); Pieper, Claus Christian; Wilhelm, Kai E.; Schild, Hans Heinz [University of Bonn, Department of Radiology, Bonn (Germany); Ezziddin, Samer; Ahmadzadehfar, Hojjat [University of Bonn, Department of Nuclear Medicine, Bonn (Germany)

    2014-02-15

    To describe a new approach to protect nontarget healthy liver tissue using degradable starch microspheres (DSM) as a short-term embolizate during radioembolization of liver tumours with {sup 90}Y microspheres. Between December 2011 and July 2012 radioembolization was performed in 54 patients. Five of these patients (three women, two men; mean age 67 years) underwent protective temporary embolization using DSM (EmboCept {sup registered} S) of normal liver tissue that could not be excluded from the area treated by radioembolization through catheter repositioning. Clinical symptoms, laboratory findings, preinterventional imaging, and {sup 99m}Tc-MAA and bremsstrahlung SPECT/CT, as well as baseline and follow-up imaging with {sup 18}F-FDG PET/CT and MRI, were evaluated in relation to the technical and clinical success of the protective embolization. Temporary embolization of arteries supplying normal liver tissue using DSM was technically successful in all five patients. {sup 99m}Tc-MAA SPECT/CT performed in the first two patients after DSM injection showed no increased pulmonary shunting compared to the MAA test injection without DSM. Bremsstrahlung SPECT/CT after radioembolization demonstrated satisfactory irradiation of the tumour and successful protection of normal liver tissue. There were only mild hepatotoxic effects (grade 1) on laboratory follow-up examinations, and no adverse events associated with DSM embolization or radioembolization were recorded. Temporary embolization with DSM before radioembolization is feasible and can effectively protect areas of normal liver tissue from irradiation and avoid permanent embolization if other methods such as catheter repositioning are not possible due to the location of the metastases. (orig.)

  17. Cellular proliferation and infiltration following interstitial irradiation of normal dog brain is altered by an inhibitor of polyamine synthesis

    International Nuclear Information System (INIS)

    Fike, John R.; Gobbel, Glenn T.; Chou, Dean; Wijnhoven, Bas P. L.; Bellinzona, Mattia; Nakagawa, Minoru; Seilhan, Theresa M.

    1995-01-01

    Purpose: The objectives of this study were to quantitatively define proliferative and infiltrative cell responses after focal 125 I irradiation of normal brain, and to determine the effects of an intravenous infusion of α-difluoromethylornithine (DFMO) on those responses. Methods and Materials: Adult beagle dogs were irradiated using high activity 125 I sources. Saline (control) or DFMO (150 mg/kg/day) was infused for 18 days starting 2 days before irradiation. At varying times up to 8 weeks after irradiation, brain tissues were collected and the cell responses in and around the focal lesion were quantified. Immunohistochemical stains were used to label astrocytes (GFAP), vascular endothelial cells (Factor VIII), polymorphonuclear leukocytes (PMNs; MAC 387) and cells synthesizing deoxyribonucleic acid (DNA) (BrdU). Cellular responses were quantified using a histomorphometric analysis. Results: After radiation alone, cellular events included a substantial acute inflammatory response followed by increased BrdU labeling and progressive increases in numbers of capillaries and astrocytes. α-Difluoromethylornithine treatment significantly affected the measured cell responses. As in controls, an early inflammatory response was measured, but after 2 weeks there were more PMNs/unit area than in controls. The onset of measurable BrdU labeling was delayed in DFMO-treated animals, and the magnitude of labeling was significantly reduced. Increases in astrocyte and vessel numbers/mm 2 were observed after a 2-week delay. At the site of implant, astrocytes from DFMO-treated dogs were significantly smaller than those from controls. Conclusions: There is substantial cell proliferation and infiltration in response to interstitial irradiation of normal brain, and these responses are significantly altered by DFMO treatment. Although the precise mechanisms by which DFMO exerts its effects in this model are not known, the results from this study suggest that modification of radiation

  18. Effect of irradiation on the dental pulp tissues in streptozotocin-induced diabetic rats

    International Nuclear Information System (INIS)

    Kang, Ho Duk; Hwang, Eui Hwan; Lee, Sang Rae

    2005-01-01

    To observe the histological changes in the pulp tissues of mandibular molars in streptozotocin-induced diabetic rats after irradiation. The male Sprague-Dawley rats weighing approximately 250 gm were divided into four groups : control, diabetes, irradiation, and diabetes-irradiation groups. Diabetes mellitus was induced in the rats by injecting streptozotocin. Rats in control and irradiation groups were injected with citrate buffer only. After 5 days, the head and neck region of the rats in irradiation and diabetes-irradiation groups were irradiated with a single absorbed dose of 10 Gy. All the rats were sacrificed at 3, 7, 14, 21, and 28 days after irradiation. The specimen including the mandibular molars were sectioned and observed using a histopathological method. In the diabetes group, capillary dilatation was observed. However, there was no obvious morphologic alteration of the odontoblasts. In the irradiation group, generalized necrosis of the dental pulp tissues was observed. Vacuolation of the odontoblasts and dilatation of the capillaries were noted in the early experimental phases. In the diabetes-irradiation group, generalized degeneration of the dental pulp tissues was observed. Vacuolation of the dental pulp cells and the odontoblasts was noted in the late experimental phases. This experiment suggest that dilatation of the capillaries in the dental pulp tissue is induced by diabetic state, and generalized degeneration of the dental pulp tissues is induced by irradiation of the diabetic group.

  19. MR characterization of post-irradiation soft tissue edema

    International Nuclear Information System (INIS)

    Richardson, M.L.; Zink-Brody, G.C.; Patten, R.M.; Koh Wuijin; Conrad, E.U.

    1996-01-01

    Objective. Radiation therapy is often used to treat bone und soft tissue neoplasms, and commonly results in soft tissue edema in the radiation field. However, the time course, distribution and degree of this edema have not been well characterized. Our study was carried out to better define these features of the edema seen following neutron and photon radiation therapy. Results. In general, soft tissue signal intensity in the radiation field initially increased over time, peaking at about 6 months for neutron-treated patients and at about 12-18 months for photon-treated patients. Signal intensity then decreased slowly over time. However, at the end of the follow-up period, signal intensity remained elevated for most patients in both groups. Signal intensity in a particular tissue was greater and tended to persist longer on STIR sequences than on T2-weighted sequences. Survival analysis of signal intensity demonstrated much longer edema survival times for neutron-treated patients than for photon-treated patients. Signal intensity increase in the intramuscular septa persisted for much longer than for fat or muscle. A mild increase in size was noted in the subcutaneous fat and intramuscular septa. Muscle, on the other hand, showed a decrease in size following treatment. This was mild for the photon-treated group and more marked for the neutron-treated group. Conclusions. There is a relatively wide variation in the duration and degree of post-irradiation edema in soft tissues. This edema seems to persist longer in the intramuscular septa than in fat or muscle. Although the duration of follow-up was limited, our study suggests that this edema resolves in roughly half the photon-treated patients within 2-3 years post-treatment and in less than 20% of neutron-treated patients by 3-4 years post-treatment. Muscle atrophy was seen in both photon- and neutron-treated patients, but was more severe in the neutron-treated group. (orig./vhe). With 4 figs

  20. SU-D-18A-04: Quantifying the Ability of Tumor Tracking to Spare Normal Tissue

    Energy Technology Data Exchange (ETDEWEB)

    Burger, A; Buzurovic, I; Hurwitz, M; Williams, C; Lewis, J [Brigham and Women' s Hospital, Dana-Farber Cancer Center, Harvard Medical Sc, Boston, MA (United States); Mishra, P [Varian Medical Systems, Palo Alto, CA (United States); Seco, J [Mass General Hospital, Harvard Medical, Boston, MA (United States)

    2014-06-01

    Purpose: Tumor tracking allows for smaller tissue volumes to be treated, potentially reducing normal tissue damage. However, tumor tracking is a more complex treatment and has little benefit in some scenarios. Here we quantify the benefit of tumor tracking for a range of patients by estimating the dose of radiation to organs at risk and the normal tissue complication probability (NTCP) for both standard and tracking treatment plans. This comparison is performed using both patient 4DCT data and extended Cardiac-Torso (XCAT) digital phantoms. Methods: We use 4DCT data for 10 patients. Additionally, we generate digital phantoms with motion derived from measured patient long tumor trajectories to compare standard and tracking treatment plans. The standard treatment is based on the average intensity projection (AIP) of 4DCT images taken over a breath cycle. The tracking treatment is based on doses calculated on images representing the anatomy at each time point. It is assumed that there are no errors in tracking the target. The NTCP values are calculated based on RTOG guidelines. Results: The mean reduction in the mean dose delivered was 5.5% to the lungs (from 7.3 Gy to 6.9 Gy) and 4.0% to the heart (from 12.5 Gy to 12.0 Gy). The mean reduction in the max dose delivered was 13% to the spinal cord (from 27.6 Gy to 24.0 Gy), 2.5% to the carina (from 31.7 Gy to 30.9 Gy), and 15% to the esophagus (from 69.6 Gy to 58.9 Gy). The mean reduction in the probability of 2nd degree radiation pneumonitis (RP) was 8.7% (3.1% to 2.8%) and the mean reduction in the effective volume was 6.8% (10.8% to 10.2%). Conclusions: Tumor tracking has the potential to reduce irradiation of organs at risk, and consequentially reduce the normal tissue complication probability. The benefits vary based on the clinical scenario. This study is supported by Varian Medical Systems, Inc.

  1. The In Vitro Response of Tissue Stem Cells to Irradiation With Different Linear Energy Transfers

    Energy Technology Data Exchange (ETDEWEB)

    Nagle, Peter W.; Hosper, Nynke A. [Department of Cell Biology, University of Groningen, University Medical Center Groningen, Groningen (Netherlands); Department of Radiation Oncology, University of Groningen, University Medical Center Groningen, Groningen (Netherlands); Ploeg, Emily M. [Department of Cell Biology, University of Groningen, University Medical Center Groningen, Groningen (Netherlands); Goethem, Marc-Jan van [Department of Radiation Oncology, University of Groningen, University Medical Center Groningen, Groningen (Netherlands); KVI-Center for Advanced Radiation Research, University of Groningen, Groningen (Netherlands); Brandenburg, Sytze [KVI-Center for Advanced Radiation Research, University of Groningen, Groningen (Netherlands); Langendijk, Johannes A. [Department of Radiation Oncology, University of Groningen, University Medical Center Groningen, Groningen (Netherlands); Chiu, Roland K. [Department of Cell Biology, University of Groningen, University Medical Center Groningen, Groningen (Netherlands); Department of Radiation Oncology, University of Groningen, University Medical Center Groningen, Groningen (Netherlands); Coppes, Robert P., E-mail: r.p.coppes@umcg.nl [Department of Cell Biology, University of Groningen, University Medical Center Groningen, Groningen (Netherlands); Department of Radiation Oncology, University of Groningen, University Medical Center Groningen, Groningen (Netherlands)

    2016-05-01

    Purpose: A reduction in the dose, irradiated volume, and sensitivity of, in particular, normal tissue stem cells is needed to advance radiation therapy. This could be obtained with the use of particles for radiation therapy. However, the radiation response of normal tissue stem cells is still an enigma. Therefore, in the present study, we developed a model to investigate the in vitro response of stem cells to particle irradiation. Methods and Materials: We used the immortalized human salivary gland (HSG) cell line resembling salivary gland (SG) cells to translate the radiation response in 2-dimensional (2D) to 3-dimensional (3D) conditions. This response was subsequently translated to the response of SG stem cells (SGSCs). Dispersed single cells were irradiated with photons or carbon ions at different linear energy transfers (LETs; 48.76 ± 2.16, 149.9 ± 10.8, and 189 ± 15 keV/μm). Subsequently, 2D or 3D clonogenicity was determined by counting the colonies or secondary stem cell-derived spheres in Matrigel. γH2AX immunostaining was used to assess DNA double strand break repair. Results: The 2D response of HSG cells showed a similar increase in dose response to increasing higher LET irradiation as other cell lines. The 3D response of HSG cells to increasing LET irradiation was reduced compared with the 2D response. Finally, the response of mouse SGSCs to photons was similar to the 3D response of HSG cells. The response to higher LET irradiation was reduced in the stem cells. Conclusions: Mouse SGSC radiosensitivity seems reduced at higher LET radiation compared with transformed HSG cells. The developed model to assess the radiation response of SGSCs offers novel possibilities to study the radiation response of normal tissue in vitro.

  2. The In Vitro Response of Tissue Stem Cells to Irradiation With Different Linear Energy Transfers

    International Nuclear Information System (INIS)

    Nagle, Peter W.; Hosper, Nynke A.; Ploeg, Emily M.; Goethem, Marc-Jan van; Brandenburg, Sytze; Langendijk, Johannes A.; Chiu, Roland K.; Coppes, Robert P.

    2016-01-01

    Purpose: A reduction in the dose, irradiated volume, and sensitivity of, in particular, normal tissue stem cells is needed to advance radiation therapy. This could be obtained with the use of particles for radiation therapy. However, the radiation response of normal tissue stem cells is still an enigma. Therefore, in the present study, we developed a model to investigate the in vitro response of stem cells to particle irradiation. Methods and Materials: We used the immortalized human salivary gland (HSG) cell line resembling salivary gland (SG) cells to translate the radiation response in 2-dimensional (2D) to 3-dimensional (3D) conditions. This response was subsequently translated to the response of SG stem cells (SGSCs). Dispersed single cells were irradiated with photons or carbon ions at different linear energy transfers (LETs; 48.76 ± 2.16, 149.9 ± 10.8, and 189 ± 15 keV/μm). Subsequently, 2D or 3D clonogenicity was determined by counting the colonies or secondary stem cell-derived spheres in Matrigel. γH2AX immunostaining was used to assess DNA double strand break repair. Results: The 2D response of HSG cells showed a similar increase in dose response to increasing higher LET irradiation as other cell lines. The 3D response of HSG cells to increasing LET irradiation was reduced compared with the 2D response. Finally, the response of mouse SGSCs to photons was similar to the 3D response of HSG cells. The response to higher LET irradiation was reduced in the stem cells. Conclusions: Mouse SGSC radiosensitivity seems reduced at higher LET radiation compared with transformed HSG cells. The developed model to assess the radiation response of SGSCs offers novel possibilities to study the radiation response of normal tissue in vitro.

  3. Hyaluronic Acid in Normal and Neoplastic Colorectal Tissue: Electrospray Ionization Mass Spectrometric and Fluor Metric Analysis

    Directory of Open Access Journals (Sweden)

    Ana Paula Cleto Marolla

    2016-01-01

    Conclusions: The expression of HA was found to be slightly lower in tumor tissue than in colorectal non-neoplastic mucosa, although this difference was not statistically significant. This finding probably influenced the lower expression of HA in tumor tissue than in colorectal non-neoplastic mucosa. Compared to normal tissues, HA levels are significantly increased in the tumor tissues unless they exhibit lymph node metastasis. Otherwise, the expression of HA in tumor tissue did not correlated with the other clinicopathological parameters.

  4. Effects of low dose irradiation on NK activity of normal individuals and patients with cancer

    International Nuclear Information System (INIS)

    Tian Hailin; Su Liaoyuan

    1994-10-01

    Effects of low dose irradiation on NK activity of lymphocytes and on K 562 cells were studied. The NK activity was determined by means of 3 H-TdR release assay. While 3 H-TdR incorporation was used to reflect functional changes of K 562 cells after low dose irradiation. 21 patients with cancer and 10 normal individuals were detected. The results indicated that the NK activity of lymphocytes in normal individuals increased significantly after 10 and 50 cGy γ-ray irradiation, while in patients with cancer the NK activity of lymphocytes increased only at the dose of 50 cGy irradiation. The increase of NK activity in normal individuals was higher than that in patients with cancer after same doses of irradiation. When K 562 cells were irradiated by 10 cGy γ-rays, the 3 H-TdR incorporation value increased. After exposed to over 50 cGy the stimulating effect disappeared

  5. Enhanced reactivation and mutagenesis of UV-irradiated adenovirus in normal human fibroblasts

    International Nuclear Information System (INIS)

    Bennett, C.B.; Rainbow, A.J.

    1988-01-01

    UV-enhanced reactivation (UVER) and UV-enhanced mutagenesis (UVEM) for two adenovirus temperature-sensitive mutants were examined following the infection of normal human fibroblasts. UV-irradiation of the virus alone resulted in dose-dependent increase in the UV-induced reversion frequency (RF) of viral progeny and a dose-dependent exponential decrease in progeny survival, when infecting non-irradiated cells. Analysis of the slopes of the UV-induced reversion curves suggested that 2.5 ± 0.3 and 2.4 ± 0.5 'hits' were required to produce a targeted reversion event among the viral progeny of Ad5ts36 and Ad5ts125 respectively. UV-irradiation of cells 24 h prior to infection resulted in a significant increase in progeny survival for UV-irradiated virus (UVER factor = 3.4 ± 0.8) concomitant with a significant increase in RF for UV-irradiated virus (targeted increase = 1.9 ± 0.3). The UV-induced RF per lethal hit to the virus was also significantly greater in UV-irradiated compared with non-irradiated cells. These results are consistent with the existence of a UV-inducible error-prone DNA repair mechanism in normal human cells. (author)

  6. Serum protein concentration in low-dose total body irradiation of normal and malnourished rats

    International Nuclear Information System (INIS)

    Viana, W.C.M.; Lambertz, D.; Borges, E.S.; Neto, A.M.O.; Lambertz, K.M.F.T.; Amaral, A.

    2016-01-01

    Among the radiotherapeutics' modalities, total body irradiation (TBI) is used as treatment for certain hematological, oncological and immunological diseases. The aim of this study was to evaluate the long-term effects of low-dose TBI on plasma concentration of total protein and albumin using prematurely and undernourished rats as animal model. For this, four groups with 9 animals each were formed: Normal nourished (N); Malnourished (M); Irradiated Normal nourished (IN); Irradiated Malnourished (IM). At the age of 28 days, rats of the IN and IM groups underwent total body gamma irradiation with a source of cobalt-60. Total protein and Albumin in the blood serum was quantified by colorimetry. This research indicates that procedures involving low-dose total body irradiation in children have repercussions in the reduction in body-mass as well as in the plasma levels of total protein and albumin. Our findings reinforce the periodic monitoring of total serum protein and albumin levels as an important tool in long-term follow-up of pediatric patients in treatments associated to total body irradiation. - Highlights: • Low-dose total body irradiation (TBI) in children have repercussions in their body-mass. • Long-term total protein and albumin levels are affected by TBI. • The monitoring of total protein and albumin levels are useful in the follow-up of TBI pediatric patients.

  7. Effects of hyperthermia and X-irradiation on mouse stromal tissue

    NARCIS (Netherlands)

    Wondergem, J.; Begg, A. C.; Haveman, J.

    1986-01-01

    The sensitivity of normal stroma to heat, irradiation and heat combined with irradiation has been studied using the tumour bed effect (TBE) assay. Irradiation before implantation led to a TBE. This TBE was dose dependent below 15 Gy, the TBE remaining relatively constant above 15 Gy. The interval

  8. Normal tissue tolerance to external beam radiation therapy: The stomach

    International Nuclear Information System (INIS)

    Oberdiac, P.; Mineur, L.

    2010-01-01

    In the following article, we will discuss general issues relating to acute and late gastric's radiation toxicities. The tolerance of the stomach to complete or partial organ irradiation is more un-appreciated than for most other organs. We consulted the Medline database via PubMed and used the key words gastric - radiotherapy - toxicity. Currently, 60 Gy or less is prescribed in gastric radiation therapy. Acute clinical toxicity symptoms are predominantly nausea and vomiting. Although there is a general agreement that the whole stomach tolerance is for doses of 40 to 45 Gy without unacceptable complication, it is well established that a stomach dose of 35 Gy increases the risk of ulcer complications. (authors)

  9. Tissue transglutaminase in normal and abnormal wound healing: review article

    OpenAIRE

    Verderio, EAM; Johnson, T; Griffin, M

    2004-01-01

    A complex series of events involving inflammation, cell migration and proliferation, ECM stabilisation and remodelling, neovascularisation and apoptosis are crucial to the tissue response to injury. Wound healing involves the dynamic interactions of multiple cells types with components of the extracellular matrix (ECM) and growth factors. Impaired wound healing as a consequence of aging, injury or disease may lead to serious disabilities and poor quality of life. Abnormal wound healing may al...

  10. Iso-effect tables and therapeutic ratios for epidermoid cancer and normal tissue stroma

    International Nuclear Information System (INIS)

    Cohen, L.; Creditor, M.

    1983-01-01

    Available literature on radiation injury to normal tissue stroma and ablation of epidermoid carcinoma was surveyed. Computer programs (RAD3 and RAD1) were then used to derive cell kinetic parameters and generate iso-effect tables for the relevant tissues. The two tables provide a set of limiting doses for tolerance of normal connective tissue (16% risk of injury) and for ablation of epidermoid cancer (16% risk of recurrence) covering a wide range of treatment schedules. Calculating the ratios of normal tissue tolerance to tumor control doses for each treatment scheme provides an array of therapeutic ratios, from which appropriate treatment schemes can be selected

  11. The effects of simultaneous application of ultrasound and ionizing radiation on cultured mammalian cells and normal tissues

    International Nuclear Information System (INIS)

    Fujita, Shozo

    1976-01-01

    The influence of therapeutic ultrasound on ionizing radiation effects was studied. Cultured mammalian cells, FM3A, and normal tissues, auricle and kidney of rabbits, were irradiated with ionizing radiation alone, ultrasound alone and both simultaneously. The biological experiments were conducted on the basis of the investigations about the physical and the chemical aspects of ultrasound. The results obtained from such a systematic study were as follows. It was considered that so called ''cavitation'' with bubble formation played an important role on the chemical effects of ultrasound. The chemical effect showed an intensity threshold in the range from 0.5 to 1 W/cm 2 . In the biological studies of ultrasound, the following must be considered; (1) the inhomogeneity of ultrasound intensity on the same plane (2) the distance between ultrasound transducer and sample. At a distance of 3 cm, the radiosensitizing effect due to simultaneous irradiation of x-rays and ultrasound on cells in suspension was detected at intensities above 2 W/cm 2 . The KI starch system in solution also showed a similar tendency. The irreversible tissue destruction was observed in the auricle irradiated with 690 R of 60 Co gamma-rays with simultaneous ultrasound at an intensity of 3 W/cm 2 for 15 minutes. However, no irreversible damage was recognized in the separate treatments with a dose four times of the combined irradiation. The interstitial nephritis was found in the kidney irradiated with 200 R of gamma-rays with simultaneous ultrasound for 5 minutes. No histological change was detectable in the separate treatments with a dose three times of the combined irradiation. The results seem to indicate that the ionizing radiation effects are enhanced by therapeutic ultrasound. (auth.)

  12. Normal tissue tolerance to external beam radiation therapy: Skin

    International Nuclear Information System (INIS)

    Ginot, A.; Doyen, J.; Hannoun-Levi, J.M.; Courdi, A.

    2010-01-01

    Acute skin toxicity is frequent during radiation therapy and can lead to temporary arrest of the treatment. Chronic toxicity can occur and conduct to cosmetic problems. Alopecia is the most frequent toxicity concerning hair and is most of the time reversible. Several factors linked to patients influence skin toxicity, such as under-nutrition, old age, obesity, smoking, skin diseases, autoimmune diseases, failure of DNA reparation. Skin, hair and nail toxicities depend also on radiation schedule. Acute toxicity is greater when dose per fraction increases. Chronic and acute toxicities are more often when total dose increases. Under 45 Gy, the risk of severe skin toxicity is low, and begins above 50 Gy. Skin toxicity depends also on the duration of radiotherapy and split course schedules are associated with less toxicities. Irradiation surface seems to influence skin toxicity but interaction is more complex. Reirradiation is often feasible in case of cancer recurrence but with a risk of grade 3-4 toxicity above all in head and neck cancer. The benefit/risk ratio has to be always precisely evaluated. Permanent alopecia is correlated with the follicle dose. Modern techniques of radiation therapy allow to spare skin. (authors)

  13. Early radiation changes of normal dog brain following internal and external brain irradiation: A preliminary report

    International Nuclear Information System (INIS)

    Chin, H.; Maruyama, Y.; Markesbery, W.; Goldstein, S.; Wang, P.; Tibbs, P.; Young, B.; Feola, J.; Beach, L.

    1984-01-01

    To examine radiation-induced changes in the normal brain, internal or external radiation was given to normal dog brain. Seven medium-sized dogs were used in this study. Two dogs were controls and an ice-pick (plastic implant applicator) was placed in the right frontal lobe for about 5 hours but no irradiation. Two dogs underwent Cs-137 brain implantation for 4 and 5 hours, respectively using an ice-pick technique. Two dogs were given internal neutron irradiation using the same technique of intracerebral ice-pick brachytherapy. One dog received an external photon irradiation using 6-Mev Linear Accelerator. Postmortem microscopic examination was made to study the early cerebral changes to irradiation in three dogs: one control with no irradiation; one received intracerebral Cesium implantation; and one external photon irradiation. Vascular change was the most prominent microscopic finding. There were hemorrhage, endothelial proliferation and fibrinoid changes of small vessel wall. Most of the changes were localized in the white matter and the cortex remained intact. Details (CT, NMR and histological studies) are discussed

  14. Effects of experimental radiotherapy and hyperthermia on tumors and normal tissues in small animals

    International Nuclear Information System (INIS)

    Wondergem, J.

    1985-01-01

    Experiments on responses of tumors, implanted subcutaneously in the leg, to irradiation alone or combined with heat are reported. The influence of factors modifying the fraction of hypoxic cells (e.g. anesthesia of the animal and tumor volume) is also discussed. The radiosensitivity of developing lung tumors was examined for spontaneous as well as for artificial lung metastases. Both experimental tumor models were compared with regard to their value in experimental radiotherapy. Data obtained on the response of artificial metastases and lung tissue to combined treatment with irradiation and several drugs are presented. Data on damage of the mouse foot, as a result of heat and/or irradiation treatments are presented. In particular the influence of thermotolerance on thermal enhancement of the radiation induced skin reaction was studied. Tolerance of the skin of previously irradiated mice to retreatment with irradiation, to hyperthermia alone and combined with X-rays was assessed. (Auth.)

  15. Pathway-specific differences between tumor cell lines and normal and tumor tissue cells

    Directory of Open Access Journals (Sweden)

    Tozeren Aydin

    2006-11-01

    Full Text Available Abstract Background Cell lines are used in experimental investigation of cancer but their capacity to represent tumor cells has yet to be quantified. The aim of the study was to identify significant alterations in pathway usage in cell lines in comparison with normal and tumor tissue. Methods This study utilized a pathway-specific enrichment analysis of publicly accessible microarray data and quantified the gene expression differences between cell lines, tumor, and normal tissue cells for six different tissue types. KEGG pathways that are significantly different between cell lines and tumors, cell lines and normal tissues and tumor and normal tissue were identified through enrichment tests on gene lists obtained using Significance Analysis of Microarrays (SAM. Results Cellular pathways that were significantly upregulated in cell lines compared to tumor cells and normal cells of the same tissue type included ATP synthesis, cell communication, cell cycle, oxidative phosphorylation, purine, pyrimidine and pyruvate metabolism, and proteasome. Results on metabolic pathways suggested an increase in the velocity nucleotide metabolism and RNA production. Pathways that were downregulated in cell lines compared to tumor and normal tissue included cell communication, cell adhesion molecules (CAMs, and ECM-receptor interaction. Only a fraction of the significantly altered genes in tumor-to-normal comparison had similar expressions in cancer cell lines and tumor cells. These genes were tissue-specific and were distributed sparsely among multiple pathways. Conclusion Significantly altered genes in tumors compared to normal tissue were largely tissue specific. Among these genes downregulation was a major trend. In contrast, cell lines contained large sets of significantly upregulated genes that were common to multiple tissue types. Pathway upregulation in cell lines was most pronounced over metabolic pathways including cell nucleotide metabolism and oxidative

  16. Drosophila Wnt and STAT Define Apoptosis-Resistant Epithelial Cells for Tissue Regeneration after Irradiation.

    Directory of Open Access Journals (Sweden)

    Shilpi Verghese

    2016-09-01

    Full Text Available Drosophila melanogaster larvae irradiated with doses of ionizing radiation (IR that kill about half of the cells in larval imaginal discs still develop into viable adults. How surviving cells compensate for IR-induced cell death to produce organs of normal size and appearance remains an active area of investigation. We have identified a subpopulation of cells within the continuous epithelium of Drosophila larval wing discs that shows intrinsic resistance to IR- and drug-induced apoptosis. These cells reside in domains of high Wingless (Wg, Drosophila Wnt-1 and STAT92E (sole Drosophila signal transducer and activator of transcription [STAT] homolog activity and would normally form the hinge in the adult fly. Resistance to IR-induced apoptosis requires STAT and Wg and is mediated by transcriptional repression of the pro-apoptotic gene reaper. Lineage tracing experiments show that, following irradiation, apoptosis-resistant cells lose their identity and translocate to areas of the wing disc that suffered abundant cell death. Our findings provide a new paradigm for regeneration in which it is unnecessary to invoke special damage-resistant cell types such as stem cells. Instead, differences in gene expression within a population of genetically identical epithelial cells can create a subpopulation with greater resistance, which, following damage, survive, alter their fate, and help regenerate the tissue.

  17. Chromosomal Aberrations in Normal and AT Cells Exposed to High Dose of Low Dose Rate Irradiation

    Science.gov (United States)

    Kawata, T.; Shigematsu, N.; Kawaguchi, O.; Liu, C.; Furusawa, Y.; Hirayama, R.; George, K.; Cucinotta, F.

    2011-01-01

    Ataxia telangiectasia (A-T) is a human autosomally recessive syndrome characterized by cerebellar ataxia, telangiectases, immune dysfunction, and genomic instability, and high rate of cancer incidence. A-T cell lines are abnormally sensitive to agents that induce DNA double strand breaks, including ionizing radiation. The diverse clinical features in individuals affected by A-T and the complex cellular phenotypes are all linked to the functional inactivation of a single gene (AT mutated). It is well known that cells deficient in ATM show increased yields of both simple and complex chromosomal aberrations after high-dose-rate irradiation, but, less is known on how cells respond to low-dose-rate irradiation. It has been shown that AT cells contain a large number of unrejoined breaks after both low-dose-rate irradiation and high-dose-rate irradiation, however sensitivity for chromosomal aberrations at low-dose-rate are less often studied. To study how AT cells respond to low-dose-rate irradiation, we exposed confluent normal and AT fibroblast cells to up to 3 Gy of gamma-irradiation at a dose rate of 0.5 Gy/day and analyzed chromosomal aberrations in G0 using fusion PCC (Premature Chromosomal Condensation) technique. Giemsa staining showed that 1 Gy induces around 0.36 unrejoined fragments per cell in normal cells and around 1.35 fragments in AT cells, whereas 3Gy induces around 0.65 fragments in normal cells and around 3.3 fragments in AT cells. This result indicates that AT cells can rejoin breaks less effectively in G0 phase of the cell cycle? compared to normal cells. We also analyzed chromosomal exchanges in normal and AT cells after exposure to 3 Gy of low-dose-rate rays using a combination of G0 PCC and FISH techniques. Misrejoining was detected in the AT cells only? When cells irradiated with 3 Gy were subcultured and G2 chromosomal aberrations were analyzed using calyculin-A induced PCC technique, the yield of unrejoined breaks decreased in both normal and AT

  18. Normal tissue tolerance to external beam radiation therapy: Adult bone

    International Nuclear Information System (INIS)

    Sargos, P.; Mamou, N.; Dejean, C.; Henriques de Figueiredo, B.; Kantor, G.; Huchet, A.; Italiano, A.

    2010-01-01

    Radiation tolerance for bone tissue has been mostly evaluated with regard to bone fracture. Main circumstances are mandibula osteoradionecrosis, hip and costal fracture, and patent or radiologic fractures in the treated volume. After radiation therapy of bone metastasis, the analysis of related radiation fracture is difficult to individualize from a pathologic fracture. Frequency of clinical fracture is less than 5% in the large series or cohorts and is probably under-evaluated for the asymptomatic lesions. Women older than 50 years and with osteoporosis are probably the main population at risk. Dose-effect relations are difficult to qualify in older series. Recent models evaluating radiations toxicity on diaphysa suggest an important risk after 60 Gy, for high dose-fraction and for a large volume. (authors)

  19. Pathologic characteristics of gut-associated lymphoid tissues and lymphocyte apoptosis in mouse intestine after neutron-and γ-irradiation

    International Nuclear Information System (INIS)

    Fu Kaifei; Peng Ruiyun; Gao Yabing; Wang Dewen; Chen Haoyu; Wu Xiaohong; Yang Yi; Hu Wenhua; Ma Junjie

    2004-01-01

    Objective: To compare the pathologic characteristics of gut-associated lymphoid tissues and lymphocyte apoptosis in neutron-irradiated mouse small intestines with those in γ-irradiated ones. Methods: Altogether 350 BALB/c mice were irradiated with different doses of neutrons or γ-rays, and were sacrificed on 6 h,12 h,125 d, 7 d, 14 d, 21 d and 28 d after irradiation and their total intestines were removed. Then the pathologic changes and death mode of lymphocytes in gut-associated lymphoid tissues were studied comparatively with light microscopy, electron microscopy and in situ terminal labeling method. Results: The basic pathologic changes of gut-associated lymphoid tissues after neutron irradiation included degeneration, apoptosis and necrosis of lymphocytes. The number of lymphocytes also decreased. There was no obvious regeneration after 4.0 and 5.5 Gy neutron irradiation, while after 2.5 Gy regeneration and recovery appeared, which were, there fore, dose-dependent. In the 2.5 Gy neutron group, the numbers of lymphocytes of intramucosal and submucous lymphoid tissues decreased, and karyopyknosis and a great quantity of nuclear fragments could also be observed at 6 h-3 d after irradiation. However, on the 3rd day regeneration of crypt epithelial cells appeared. On the 5th day hyperplasia of submucous lymphocytic tissues appeared, but recovery to normal level was not achieved till 14 d after irradiation. The basic pathologic changes after γ-irradiation were similar to that of neutron irradiation. Regeneration and recovery appeared in the 5.5 Gy group while no obvious regeneration in the 12.0 Gy group. The results of in situ terminal labeling indicated that at 6 h after irradiation the number of apoptotic cells in gut-associated lymphoid tissues of each group increased obviously, while in 4.0 Gy neutron group and 12.0 Gy γ-ray group it was more abundant. Conclusion: Both 2.5-5.5 Gy neutron and 5.5-12.0 Gy γ-ray irradiation can induce obvious injuries in gut

  20. Normalization of periodontal tissues in osteopetrotic mib mutant rats, treated with CSF-1

    Science.gov (United States)

    Wojtowicz, A.; Yamauchi, M.; Sotowski, R.; Ostrowski, K.

    1998-01-01

    The osteopetrotic mib mutation in rats causes defects in the skeletal bone tissue in young animals. These defects, i.e. slow bone remodelling, changes in both crystallinity and mineral content, are transient and undergo normalization, even without any treatment in 6-wk-old animals. Treatment with CSF-1 (colony stimulating factor-1) accelerates the normalization process in skeletal bones. The periodontal tissues around the apices of incisors show abnormalities caused by the slow remodelling process of the mandible bone tissue, the deficiency of osteoclasts and their abnormal morphology, as well as the disorganization of periodontal ligament fibres. In contrast to the skeletal tissues, these abnormalities would not undergo spontaneous normalization. Under treatment with colony stimulating factor 1 (CSF-1), the primitive bone trabeculae of mandible are resorbed and the normalization of the number of osteoclasts and their cytology occurs. The organization of the periodontal ligament fibres is partially restored, resembling the histological structure of the normal one.

  1. Modulation of antioxidant enzymes as radioprotector mechanism of oligo elements and lachesis muta in normal tissues

    International Nuclear Information System (INIS)

    Crescenti, E.; Croci, M.; Mohamad, N.; Medina, V.; Sambuco, L.; Gutierrez, A.; Nunez, M.; Martin, G.; Cricco, G.; Bergoc, R.; Rivera, E.

    2006-01-01

    The therapeutic use of the ionizing radiations (IR) it has acquired great relevance in the last decades although their effects are not selective and they are also manifested on the normal tissues. In previous works we demonstrate the radioprotector effect that the combination of oligo elements Zinc, Selenium and Manganese associated to the snake poison Lachesis muta (O-LM) it exercises on the small intestine and the bone marrow of irradiated mouse. The objective of this work was to study the molecular mechanisms, and particularly the paper of the anti-oxidant superoxide dismutases enzymes (MnSOD and Cu/ZnSOD), Catalase (CAT), and Glutathione Peroxidase (GPx), in the radioprotector action that exercises the combination O-LM. Four groups of mice were used: A) control; B) treated with O-LM; C) irradiated; D) irradiated and treated with O-LM. The two treated groups were injected daily via s.c. with 0,1 ml of O-LM from 30 days before the irradiation and until to 4 days later. The two irradiated groups received 10 Gy in whole body the day 30. The day 35 all the animals were sacrificed. The histological intestinal cuts of the mucous one were evaluated by tint with hematoxyline-eosin; the presence of apoptotic cells it was determined by the Tunel method (Apoptag kit); the expression of PCNA (nuclear antigen of proliferating cells), MnSOD, CuZnSOD, CAT and GPx, by immunohistochemistry. The results demonstrated that in the lot D it was preserved totally the histology of the intestinal mucous. In the control A it was observed PCNA expression in the crypts, of MnSOD in the hairiness and CuZnSOD, CAT and Gpx in both. The change produced by O-LM (group B) it was the increase of PCNA, of CAT and the appearance of MnSOD in the crypts. On the other hand, the irradiation (C) it produced a marked descent in the GPx, the complete disappearance of PCNA and an increase of the apoptotic cells. The group D showed that O-LM it reverted totally the effect of the RI on the expression of PCNA

  2. Revascularization of autogenous skin grafts placed on irradiated tissue

    International Nuclear Information System (INIS)

    Ueda, M.; Torii, S.; Kaneda, T.; Oka, T.

    1982-01-01

    Vascular changes in rat skin after irradiation were examined microangiographically. Revascularization of the skin transplanted during the chronic stage after irradiation was also studied. The results obtained through these examinations revealed higher vascular densities at the acute and the subacute stages, and low values at the chronic stages compared with those of the control. Furthermore, when the skin grafts were transplanted to the irradiated beds in the chronic stage, primary revascularization was scant, and the inhibited capillary proliferation in the recipient sites prevented new vessel penetration. This explains why grafts transplanted to previously irradiated beds fail to survive

  3. Trace metal physiology in normal and pathological tissues

    International Nuclear Information System (INIS)

    Hamer, C.J.A. van den; Nooijen, J.L.

    1979-01-01

    Many of the ionic tumour seeking radiopharmaceuticals consist of a metal ion combined with an anion. The choice of metal depends on the existence of radionuclides with suitable radiological properties, and on their availability. Because several of the metal complexes used in nuclear medicine are of rather recent interest, information about their metabolism is scarce. Although nuclear medicine is limited to those metals which radiochemists can produce, we can manipulate the chemical form in which the metals are introduced into the organism to some extent. The relation between chemical form and biological pathway, e.g., the extent of accumulation in certain tissues, is subject of study related to trace metal physiology. It is the purpose of this paper to try and bridge the gap between nuclear medicine and trace metal physiology by showing the progress made by the latter in the study of the metabolism of copper and zinc. Few trace metals have been studied as thoroughly as these, although iron could have been chosen just as well. This presentation is limited to a study of the fate of a metal derivative after its intravenous injection. Where possible the results obtained are related to the behaviour of metals presently of interest to nuclear medicine. (Auth.)

  4. Proteinase-activated receptors - mediators of early and delayed normal tissue radiation responses

    International Nuclear Information System (INIS)

    Hauer-Jensen, M.

    2003-01-01

    Proteinase-activated receptors (PARs) are G-protein coupled receptors that are activated by proteolytic exposure of a receptor-tethered ligand. The discovery of this receptor family represents one of the most intriguing recent developments in signal transduction. PARs are involved in the regulation of many normal and pathophysiological processes, notably inflammatory and fibroproliferative responses to injury. Preclinical studies performed in our laboratory suggest that proteinase-activated receptor-1 (PAR-1) plays a critical role in the mechanism of chronicity of radiation fibrosis, while proteinase-activated receptor-2 (PAR-2) may mediate important fibroproliferative responses in irradiated intestine. Specifically, activation of PAR-1 by thrombin, and PAR-2 by pancreatic trypsin and mast cell proteinases, appears to be involved in acute radiation-induced inflammation, as well as in subsequent extracellular matrix deposition, leading to the development of intestinal wall fibrosis and clinical complications. Pharmacological modulators of PAR-1 or PAR-2 expression or activation would be potentially useful as preventive or therapeutic agents in patients who receive radiation therapy, especially if blockade could be targeted to specific tissues or cellular compartments

  5. Raman spectroscopy of normal oral buccal mucosa tissues: study on intact and incised biopsies

    Science.gov (United States)

    Deshmukh, Atul; Singh, S. P.; Chaturvedi, Pankaj; Krishna, C. Murali

    2011-12-01

    Oral squamous cell carcinoma is one of among the top 10 malignancies. Optical spectroscopy, including Raman, is being actively pursued as alternative/adjunct for cancer diagnosis. Earlier studies have demonstrated the feasibility of classifying normal, premalignant, and malignant oral ex vivo tissues. Spectral features showed predominance of lipids and proteins in normal and cancer conditions, respectively, which were attributed to membrane lipids and surface proteins. In view of recent developments in deep tissue Raman spectroscopy, we have recorded Raman spectra from superior and inferior surfaces of 10 normal oral tissues on intact, as well as incised, biopsies after separation of epithelium from connective tissue. Spectral variations and similarities among different groups were explored by unsupervised (principal component analysis) and supervised (linear discriminant analysis, factorial discriminant analysis) methodologies. Clusters of spectra from superior and inferior surfaces of intact tissues show a high overlap; whereas spectra from separated epithelium and connective tissue sections yielded clear clusters, though they also overlap on clusters of intact tissues. Spectra of all four groups of normal tissues gave exclusive clusters when tested against malignant spectra. Thus, this study demonstrates that spectra recorded from the superior surface of an intact tissue may have contributions from deeper layers but has no bearing from the classification of a malignant tissues point of view.

  6. Long-term changes in cell population kinetics of skin tissue after local beta-irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Yamaguchi, T [National Inst. of Radiological Sciences, Chiba (Japan)

    1975-06-01

    Using /sup 3/H-thymidine autoradiography, long-term alterations in cell kinetics were studied in guinea pig skin after ..beta..irradiation with 3000 rads. After complete depopulation, epidermal basal cells at the radiation margin became proliferative 10 days postirradiation and spread over the depopulated area. When epithelization (20 days) was complete the cell cycle time of the basal cells reverted to normal, but the differentiation rate was much slower than that in unirradiated skin. This appeared to be a cause of the persistent (acanthotic) hyperplasia. Similar but slower changes were found in dermal tissue. Reparative proliferation of fibroblasts and capillary endothelial cells began at 20 and 30 days, respectively. Active fibroblastic proliferation was found as late as 110 days. This, along with the abortive nature of the reparative angiogenesis, seemed to be a cause of the later fibrosis (150 to 400 days).

  7. A normalization of the physical tests for external irradiation measuring detectors

    International Nuclear Information System (INIS)

    1977-05-01

    This report is the result of a normalization work, realized within the Radioprotection Services of the C.E.A., of the physical tests for detectors measuring external irradiation. Among the various tests mentionned are treated more in details, calibration and the establishment of the relative spectral response. As far as calibration is concerned, the normalization refers to: the reference detector, the reference radiation source, the installation and calibration procedure. As for the relative spectral response the normalization refers to: the reference detector, the radiation sources to be used. Finally, a chapter is consecrated to the high flux detectors and to those for pulsed electromagnetic radiations [fr

  8. Study on electric parameters of wild and cultivated cotton forms being in normal state and irradiated

    International Nuclear Information System (INIS)

    Nazirov, N.N.; Kamalov, N.; Norbaev, N.

    1978-01-01

    The radiation effect on electric conductivity of tissues in case of alternating current, electrical capacity and cell impedance has been studied. Gamma irradiation of seedlings results in definite changes of electric factors of cells (electric conductivity, electric capacity, impedance). It is shown that especially strong changes have been revealed during gamma irradiation of radiosensitive wild form of cotton plants. The deviation of cell electric factors from the standard depends on the violation of evolutionally composed ion heterogeneity and cell colloid system state, which results in changes in their structure and metabolism in them

  9. Expression of UV-irradiated adenovirus in normal and UV-sensitive Chinese hamster ovary cells

    International Nuclear Information System (INIS)

    Rainbow, A.J.

    1985-01-01

    The chinese hamster ovary (CHO) cell mutants UV-20, UV-24, and UV-41 are abnormally sensitive to UV and harbour various defects lin their ability to repair cellular DNA. This study has examined the expression of UV-irradiated AD2 in these cells. HCR of UV-irradiated Ad2, as measured by viral structural antigen (Vag) formation or progeny production, was found to be similar for the normal and the UV-sensitive CHO strains. UV-irradiation of Ad2 (1200 J/m/sup 2/) resulted in a delay of Vag expression of 18 hours in normal human fibroblasts, which is thought to reflect the time required for removal of UV-induced lesions from the DNA before viral DNA synthesis can proceed. However, a similar UV-irradiation of Ad2 did not result in a delay of Vag expression for infection of CHO cells, suggesting that UV-induced lesions in Ad2 DNA do not inhibit its replication in CHO cells. These results indicate a fundamental difference in the processing of UV-irradiated AD2-DNA in CHO as compared to human cells

  10. Discriminant analysis of normal and malignant breast tissue based upon INAA investigation of elemental concentration

    International Nuclear Information System (INIS)

    Kwanhoong Ng; Senghuat Ong; Bradley, D.A.; Laimeng Looi

    1997-01-01

    Discriminant analysis of six trace element concentrations measured by instrumental neutron activation analysis (INAA) in 26 paired-samples of malignant and histologically normal human breast tissues shows the technique to be a potentially valuable clinical tool for making malignant-normal classification. Nonparametric discriminant analysis is performed for the data obtained. Linear and quadratic discriminant analyses are also carried out for comparison. For this data set a formal analysis shows that the elements which may be useful in distinguishing between malignant and normal tissues are Ca, Rb and Br, providing correct classification for 24 out of 26 normal samples and 22 out of 26 malignant samples. (Author)

  11. Comparison of Tissue Stiffness Using Shear Wave Elastography in Men with Normal Testicular Tissue, Testicular Microlithiasis and Testicular Cancer

    DEFF Research Database (Denmark)

    Pedersen, Malene Roland; Møller, Henrik; Osther, Palle Jørn Sloth

    2017-01-01

    Objectives: To compare elastography measurements in men with normal testicular tissue, testicular microlithiasis and testicular cancer. Methods: A total of 248 consecutive patients were included. All men provided written informed consent. Testicular stiffness was assessed using shear wave...... elastography (SWE). Three SWE velocity measurements were assessed in each testicle. The patients were divided into three groups; men with normal testicular tissue (n=130), men with testicular microlithiasis (n=99) and men with testicular cancer (n=19). Results: We found a higher mean velocity in the group...... of patients with testicular cancer (1.92 m/s (95% CI 1.82-2.03)) compared to both the group with normal tissue (0.76 m/s (95% CI: 0.75-0.78)) (ptesticular microlithiasis 0.79 m/s (95% CI: 0.77-0.81) (ptesticular microlithiasis increased stiffness...

  12. Influence of trichlorfon and fractionated irradiation on hydroproteolytic activity of pancreas and intestinal tissues of rats

    Energy Technology Data Exchange (ETDEWEB)

    Kocmierska-Grodzka, D [Akademia Medyczna, Bialystok (Poland). Zaklad Farmakologii

    1976-03-01

    Investigations were carried out of the hydroproteolytic activity of pancreas, small intestine and colon of rats after fractionated irradiation (5x150 R). Marked postirradiation enhancement of lipase activity was found in pancreas and duodenal part of intestine as well as an increase of B-glucuronidase and acid phosphatase activity in nearly all parts of the intestinal tissues. Fractionated irradiation resulted in an increase of pancreatic catheptic (proteolytic) activity, causing simultaneous decrease of proteolytic activity in intestine and colon. Preventive administation of Trichlorfon ten days before irradiation (10 mg or 30 mg/kg) evoked modification of hydroproteolytic activity in intestinal tissues of healthy and irradiated rats. 30mg/kg Trichlorfon exerted antilipolytic and anticatheptic effects in pancreas and intestinal tissues of irradiated rats.

  13. Superconducting and normal state properties of carbon doped and neutron irradiated MgB2

    International Nuclear Information System (INIS)

    Wilke, R.H.T.; Samuely, P.; Szabo, P.; Holanova, Z.; Bud'ko, S.L.; Canfield, P.C.; Finnemore, D.K.

    2007-01-01

    Current research in MgB 2 focuses on the effects various types of perturbations have on the superconducting properties of this novel two-gap superconductor. In this article we summarize the effects of carbon doping and neutron irradiation in bulk MgB 2 . Low levels of carbon doping and light neutron irradiation result in significant enhancements in H c2 . At high fluences, where superconductivity is nearly fully suppressed, superconductivity can be restored through post exposure annealing. However, this results in a change in the interdependencies of the normal state and superconducting properties (ρ 0 , T c , H c2 ), with little or no enhancement in H c2

  14. Stem cell therapy for the treatment of radiation-induced normal tissue damage

    International Nuclear Information System (INIS)

    Chapel, A.; Benderitter, M.; Gourmelon, P.; Lataillade, J.J.; Gorin, N.C.

    2013-01-01

    Radiotherapy may induce irreversible damage on healthy tissues surrounding the tumour. In Europe, per year, 1.5 million patients undergo external radiotherapy. Acute adverse effect concern 80% of patients. The late adverse effect of radiotherapy concern 5 to 10% of them, which could be life threatening. Eradication of these manifestations is crucial. The French Institute of Radioprotection and Nuclear Safety (IRSN) contribute to understand effect of radiation on healthy tissue. IRSN is strongly implicated in the field of regeneration of healthy tissue after radiotherapy or radiological accident and in the clinical use of cell therapy in the treatment of irradiated patients. Our first success in cell therapy was the correction of deficient hematopoiesis in two patients. The intravenous injection of Mesenchymal Stem Cells (MSC) has restored bone marrow micro-environment after total body irradiation necessary to sustain hematopoiesis. Cutaneous radiation reactions play an important role in radiation accidents, but also as a limitation in radiotherapy and radio-oncology. We have evidenced for the first time, the efficiency of MSC therapy in the context of acute cutaneous and muscle damage following irradiation in five patients. Concerning the medical management of gastrointestinal disorder after irradiation, we have demonstrated the promising approach of the MSC treatment. We have shown that MSC migrate to damaged tissues and restore gut functions after radiation damage. The evaluation of stem cell therapy combining different sources of adult stem cells is under investigation

  15. Tissue repair capacity and repair kinetics deduced from multifractionated or continuous irradiation regimens with incomplete repair

    International Nuclear Information System (INIS)

    Thames, H.D. Jr.; Peters, L.J.

    1984-01-01

    A model is proposed for cell survival after multiple doses, when the interfraction interval is insufficient for complete Elkind repair. In the limit of ever-increasing number of ever-smaller fractional doses, the model transforms into the accumulation model of survival after continuous irradiation. When adapted to describe tissue responses to isoeffective multifractionated regimens, wherein repair is incomplete, a generalization of the usually linear plot of reciprocal total dose versus dose per fraction is obtained, in which downward curvature is evident. There is an advantage in studying tissue responses to multifractionated regimens with incomplete repair in the interfraction intervals, or continuous exposures at various dose rates since, in addition to determination of repair capacity, there is an estimate of repair kinetics. Results of analyses of previously published data are presented as illustration. Estimated from the response of three acutely responding normal tissues in the mouse (jejunum, colon and bone marrow), repair halftimes ranged from 0.3-0.9 h and values of β/delta were approximately 0.1 Gy -1 . From the response of mouse lung (LD50 for pneumonitis) to multifractionated regimens with incomplete repair, the repair halftime was estimated at 1.5 h and β/delta was 0.27 Gy -1 . In the rat spinal cord β/delta was 0.7 Gy -1 and Tsub(1/2) was 1.5 h. (U.K.)

  16. A new formula for normal tissue complication probability (NTCP) as a function of equivalent uniform dose (EUD).

    Science.gov (United States)

    Luxton, Gary; Keall, Paul J; King, Christopher R

    2008-01-07

    To facilitate the use of biological outcome modeling for treatment planning, an exponential function is introduced as a simpler equivalent to the Lyman formula for calculating normal tissue complication probability (NTCP). The single parameter of the exponential function is chosen to reproduce the Lyman calculation to within approximately 0.3%, and thus enable easy conversion of data contained in empirical fits of Lyman parameters for organs at risk (OARs). Organ parameters for the new formula are given in terms of Lyman model m and TD(50), and conversely m and TD(50) are expressed in terms of the parameters of the new equation. The role of the Lyman volume-effect parameter n is unchanged from its role in the Lyman model. For a non-homogeneously irradiated OAR, an equation relates d(ref), n, v(eff) and the Niemierko equivalent uniform dose (EUD), where d(ref) and v(eff) are the reference dose and effective fractional volume of the Kutcher-Burman reduction algorithm (i.e. the LKB model). It follows in the LKB model that uniform EUD irradiation of an OAR results in the same NTCP as the original non-homogeneous distribution. The NTCP equation is therefore represented as a function of EUD. The inverse equation expresses EUD as a function of NTCP and is used to generate a table of EUD versus normal tissue complication probability for the Emami-Burman parameter fits as well as for OAR parameter sets from more recent data.

  17. A new formula for normal tissue complication probability (NTCP) as a function of equivalent uniform dose (EUD)

    International Nuclear Information System (INIS)

    Luxton, Gary; Keall, Paul J; King, Christopher R

    2008-01-01

    To facilitate the use of biological outcome modeling for treatment planning, an exponential function is introduced as a simpler equivalent to the Lyman formula for calculating normal tissue complication probability (NTCP). The single parameter of the exponential function is chosen to reproduce the Lyman calculation to within ∼0.3%, and thus enable easy conversion of data contained in empirical fits of Lyman parameters for organs at risk (OARs). Organ parameters for the new formula are given in terms of Lyman model m and TD 50 , and conversely m and TD 50 are expressed in terms of the parameters of the new equation. The role of the Lyman volume-effect parameter n is unchanged from its role in the Lyman model. For a non-homogeneously irradiated OAR, an equation relates d ref , n, v eff and the Niemierko equivalent uniform dose (EUD), where d ref and v eff are the reference dose and effective fractional volume of the Kutcher-Burman reduction algorithm (i.e. the LKB model). It follows in the LKB model that uniform EUD irradiation of an OAR results in the same NTCP as the original non-homogeneous distribution. The NTCP equation is therefore represented as a function of EUD. The inverse equation expresses EUD as a function of NTCP and is used to generate a table of EUD versus normal tissue complication probability for the Emami-Burman parameter fits as well as for OAR parameter sets from more recent data

  18. Impact of statistical learning methods on the predictive power of multivariate normal tissue complication probability models

    NARCIS (Netherlands)

    Xu, Cheng-Jian; van der Schaaf, Arjen; Schilstra, Cornelis; Langendijk, Johannes A.; van t Veld, Aart A.

    2012-01-01

    PURPOSE: To study the impact of different statistical learning methods on the prediction performance of multivariate normal tissue complication probability (NTCP) models. METHODS AND MATERIALS: In this study, three learning methods, stepwise selection, least absolute shrinkage and selection operator

  19. Enhancing the radiation response of tumors but not early or late responding normal tissues using a vascular disrupting agent

    DEFF Research Database (Denmark)

    Horsman, Michael R

    2017-01-01

    INTRODUCTION: Vascular disrupting agents (VDAs) damage tumor vasculature and enhance tumor radiation response. In this pre-clinical study, we combined radiation with the leading VDA in clinical development, combretastatin A-4 phosphate (CA4P), and compared the effects seen in tumors and relevant...... normal tissues. MATERIAL AND METHODS: Radiation was applied locally to tissues in CDF1 mice to produce full radiation dose-response curves. CA4P (250 mg/kg) was intraperitoneally (i.p.) injected within 30 minutes after irradiating. Response of 200 mm3 foot implanted C3H mammary carcinomas was assessed......% increase in ventilation rate measured by plethysmography within 9 months). A Chi-squared test was used for statistical comparisons (significance level of p 4P. The radiation...

  20. Histological observation on dental hard tissue irradiated by ultrashort-pulsed laser

    Science.gov (United States)

    Uchizono, Takeyuki; Awazu, Kunio; Igarashi, Akihiro; Kato, Junji; Hirai, Yoshito

    2006-04-01

    In the field of dentistry, effectiveness of USPL irradiation is researched because USPL has less thermal side effect to dental hard tissue. In this paper, we observed morphological change and optical change of dental hard tissue irradiated by USPL for discussing the safety and effectiveness of USPL irradiation to dental hard tissues. Irradiated samples were crown enamel and root dentin of bovine teeth. Lasers were Ti:sapphire laser, which had pulse duration (P d)of 130 fsec and pulse repetition rate (f) of 1kHz and wavelength (l) of 800nm, free electron laser (FEL), which had P d of 15 μsec and f of 10Hz and wavelength of 9.6μm, and Er:YAG laser, which had P d of 250 μsec and f of 10Hz and wavelength of 2.94μm. After laser irradiation, the sample surfaces and cross sections were examined with SEM and EDX. The optical change of samples was observed using FTIR. In SEM, the samples irradiated by USPL had sharp and accurate ablation with no crack and no carbonization. But, in FEL and Er:YAG laser, the samples has rough ablation with crack and carbonization. It was cleared that the P/Ca ratio of samples irradiated by USPL had same value as non-irradiated samples. There was no change in the IR absorption spectrum between samples irradiated by USPL and non-irradiated sample. But, they of samples irradiated by FEL and Er:YAG laser, however, had difference value as non-irradiated samples. These results showed that USPL might be effective to ablate dental hard tissue without thermal damage.

  1. SU-E-T-168: Evaluation of Normal Tissue Damage in Head and Neck Cancer Treatments

    International Nuclear Information System (INIS)

    Ai, H; Zhang, H

    2014-01-01

    Purpose: To evaluate normal tissue toxicity in patients with head and neck cancer by calculating average survival fraction (SF) and equivalent uniform dose (EUD) for normal tissue cells. Methods: 20 patients with head and neck cancer were included in this study. IMRT plans were generated using EclipseTM treatment planning system by dosimetrist following clinical radiotherapy treatment guidelines. The average SF for three different normal tissue cells of each concerned structure can be calculated from dose spectrum acquired from differential dose volume histogram (DVH) using linear quadratic model. The three types of normal tissues include radiosensitive, moderately radiosensitive and radio-resistant that represents 70%, 50% and 30% survival fractions, respectively, for a 2-Gy open field. Finally, EUDs for three types of normal tissue of each structure were calculated from average SF. Results: The EUDs of the brainstem, spinal cord, parotid glands, brachial plexus and etc were calculated. Our analysis indicated that the brainstem can absorb as much as 14.3% of prescription dose to the tumor if the cell line is radiosensitive. In addition, as much as 16.1% and 18.3% of prescription dose were absorbed by the brainstem for moderately radiosensitive and radio-resistant cells, respectively. For the spinal cord, the EUDs reached up to 27.6%, 35.0% and 42.9% of prescribed dose for the three types of radiosensitivities respectively. Three types of normal cells for parotid glands can get up to 65.6%, 71.2% and 78.4% of prescription dose, respectively. The maximum EUDs of brachial plexsus were calculated as 75.4%, 76.4% and 76.7% of prescription for three types of normal cell lines. Conclusion: The results indicated that EUD can be used to quantify and evaluate the radiation damage to surrounding normal tissues. Large variation of normal tissue EUDs may come from variation of target volumes and radiation beam orientations among the patients

  2. Dosimetric precision requirements and quantities for characterizing the response of tumors and normal tissues

    Energy Technology Data Exchange (ETDEWEB)

    Brahme, A [Karolinska Inst., Stockholm (Sweden). Dept. of Radiation Physics

    1996-08-01

    Based on simple radiobiological models the effect of the distribution of absorbed dose in therapy beams on the radiation response of tumor and normal tissue volumes are investigated. Under the assumption that the dose variation in the treated volume is small it is shown that the response of the tissue to radiation is determined mainly by the mean dose to the tumor or normal tissue volume in question. Quantitative expressions are also given for the increased probability of normal tissue complications and the decreased probability of tumor control as a function of increasing dose variations around the mean dose level to these tissues. When the dose variations are large the minimum tumor dose (to cm{sup 3} size volumes) will generally be better related to tumor control and the highest dose to significant portions of normal tissue correlates best to complications. In order not to lose more than one out of 20 curable patients (95% of highest possible treatment outcome) the required accuracy in the dose distribution delivered to the target volume should be 2.5% (1{sigma}) for a mean dose response gradient {gamma} in the range 2 - 3. For more steeply responding tumors and normal tissues even stricter requirements may be desirable. (author). 15 refs, 6 figs.

  3. Liver tissue tolerance for irradiation : Experimental and clinical investigations

    NARCIS (Netherlands)

    Cromheecke, M; Konings, AWT; Szabo, BG; Hoekstra, HJ

    2000-01-01

    Radiation treatment of the liver for malignant disease has gained renewed interest due to newly developed treatment modalities. Still limited specific knowledge is available concerning liver damage following irradiation. Inconsistencies between reported animal experimental studies are largely due to

  4. Radiation-induced organogenesis: effects of irradiated medium and its components on tobacco tissue culture

    International Nuclear Information System (INIS)

    Degani, N.

    1975-01-01

    Gamma irradiated medium induces the formation of buds in non-irradiated dark growth tobacco callus (Nicotiana tabacum Var. Wisconsin No.38). Experiments were conducted to determine the component(s) of the medium that is effective in this radiation-induced organogenesis. Fraction of medium were irradiated singly and in combination, then combined with non-irradiated fractions to form the complete growth medium. The results showed that irradiated indoleacetic acid (IAA) was not the effective component in the induction of organogensis. Omission of IAA from the medium resulted in the formation of buds, as expected. Irradiated myo-inositol induced organogenesis more consistently than the other irradiated components. The age of the inoculum tissue and its passage number from the tobacco stem affected the potency of the tobacco callus to organise. (author)

  5. Relationship between acute and late normal tissue injury after postoperative radiotherapy in endometrial cancer

    International Nuclear Information System (INIS)

    Jereczek-Fossa, Barbara A.; Jassem, Jacek; Badzio, Andrzej

    2002-01-01

    Purpose: To evaluate the relationship between acute and late normal tissue reactions in 317 consecutive endometrial cancer patients treated with surgery and adjuvant radiotherapy (RT). Methods: The data of 317 patients (staging according to the International Federation of Gynecology and Obstetrics) treated with postoperative RT were analyzed. Both low-dose-rate brachytherapy and external beam RT were applied in 247 patients (78%); brachytherapy only in 49 (15%) and external beam irradiation only in 21 (7%). The median follow-up was 7.3 years (range 4-21). The European Organization for Research and Treatment of Cancer, Radiation Therapy Oncology Group system with elements of the late effects of normal tissue, subjective, objective, management, analytic (LENT/SOMA) scale was used to score the RT reactions. The correlation between the occurrence and severity of acute and late bowel and bladder toxicity, as well as the relationship between the severity of acute effects and time to occurrence of late reactions, were assessed using linear and logistic regression analyses. Results: Of the 317 patients, 268 (85%) experienced acute RT reactions of any grade. Severe acute bowel reactions were observed in 15 patients (5%), urinary bladder complications in 1 patient (0.5%), cutaneous in 1 patient (0.5%), and vaginal in 1 patient (0.5%). Severe acute hematologic toxicity was seen in 3 patients (1%). A total of 158 patients (51%) experienced late RT reactions of any grade. Severe late bowel reactions were observed in 19 patients (6%), urinary bladder in 5 (2%), vaginal in 3 (1%), and bone in 10 (4%). When all toxic events were considered, there was a highly significant correlation between the acute and late bowel reactions (p <0.001), but the acute and late urinary bladder reactions did not correlate (p=0.64). The grade of acute toxicity was found to predict the grade of late toxicity for the bowel but not for the bladder (p<0.001 and p=0.47, respectively). The severity of acute

  6. The normal tissue sparing obtained with simultaneous treatment of pelvic lymph nodes and bladder using intensity-modulated radiotherapy

    International Nuclear Information System (INIS)

    Soendergaard, Jimmi; Hoeyer, Morten; Wright, Pauliina; Grau, Cai; Muren, Ludvig Paul; Petersen, Joergen B.

    2009-01-01

    We have implemented an intensity-modulated radiotherapy (IMRT) protocol for simultaneous irradiation of bladder and lymph nodes. In this report, doses to normal tissue from IMRT and our previous conformal sequential boost technique are compared. Material and methods. Sixteen patients with urinary bladder cancer were treated using a six-field dynamic IMRT beam arrangement delivering 60 Gy to the bladder and 48 Gy to the pelvic lymph nodes. Dose-volume histogram (DVH) parameters for relevant normal tissues (bowel, bowel cavity, rectum and femoral heads) for the IMRT plans were compared with corresponding DVHs from our previous conformal sequential boost technique. Calculations of the generalized Equivalent Uniform Dose (gEUD) were performed for the bowel, with a reference volume of 200 cm 3 and a volume effect parameter k = 4, as well as for the rectum, using k = 12. Acute gastrointestinal (GI) and genitourinary (GU) RTOG toxicity was recorded. Results. Statistical significant normal tissue sparing was obtained by IMRT. For the bowel, a significant reduction was obtained at all dose levels between 20 and 50 Gy (p 3 at 50 Gy, while the gEUD was reduced from 58 to 53 Gy (p 3 at 50 Gy. The rectum gEUD was reduced from 55 to 53 Gy (p < 0.05). For the femoral heads, IMRT reduced the maximum dose as well as the volumes above all dose levels. The rate of acute peak Grade 2 GI RTOG complications was 38% after IMRT. Conclusion. IMRT to the urinary bladder and elective lymph nodes result in considerable normal tissue sparing compared to conformal sequential boost technique. This has paved the way for further studies combining IMRT with image-guided radiotherapy (IGRT) in bladder cancer

  7. Effect of tumor therapeutic irradiation on the mechanical properties of teeth tissue

    International Nuclear Information System (INIS)

    Fraenzel, W.; Gerlach, R.; Hein, H.J.; Schaller, H.G.

    2006-01-01

    Tumor irradiation of the head-neck area is accompanied by the development of a so-called radiation caries in the treated patients. In spite of conservative therapeutic measures, the process results in tooth destruction. The present study investigated the effects of irradiation on the demineralization and remineralization of the dental tissue. For this purpose, retained third molars were prepared and assigned either to a test group, which was exposed to fractional irradiation up to 60 Gy, or to a non-irradiated control group. Irradiated and non-irradiated teeth were then demineralized using acidic hydroxyl-cellulose gel; afterwards the teeth were remineralized using either Bifluorid12 registered or elmex gelee registered . The nanoindentation technique was used to measure the mechanical properties, hardness and elasticity, of the teeth in each of the conditions. The values were compared to the non-irradiated control group. Irradiation decreased dramatically the mechanical parameters of enamel and dentine. In non-irradiated teeth, demineralization had nearly the same effects of irradiation on the mechanical properties. In irradiated teeth, the effects of demineralization were negligible in comparison to non-irradiated teeth. Remineralization with Bifluorid12 registered or elmex gelee registered led to a partial improvement of the mechanical properties of the teeth. The enamel was more positively affected, by remineralization than the dentine. (orig.)

  8. Effect of tumor therapeutic irradiation on the mechanical properties of teeth tissue

    Energy Technology Data Exchange (ETDEWEB)

    Fraenzel, W. [Dept. of Physics, Martin Luther Univ. Halle (Germany); Gerlach, R. [Univ. Clinic and Policlinic for Radiation Therapy, Martin Luther Univ. Halle (Germany); Hein, H.J. [Univ. Clinic and Policlinic for Orthopaedics and Physical Medicine, Martin Luther Univ. Halle (Germany); Schaller, H.G. [Dept. of Operative Dentistry and Periodontology, Martin Luther Univ. Halle (Germany)

    2006-07-01

    Tumor irradiation of the head-neck area is accompanied by the development of a so-called radiation caries in the treated patients. In spite of conservative therapeutic measures, the process results in tooth destruction. The present study investigated the effects of irradiation on the demineralization and remineralization of the dental tissue. For this purpose, retained third molars were prepared and assigned either to a test group, which was exposed to fractional irradiation up to 60 Gy, or to a non-irradiated control group. Irradiated and non-irradiated teeth were then demineralized using acidic hydroxyl-cellulose gel; afterwards the teeth were remineralized using either Bifluorid12 {sup registered} or elmex gelee {sup registered}. The nanoindentation technique was used to measure the mechanical properties, hardness and elasticity, of the teeth in each of the conditions. The values were compared to the non-irradiated control group. Irradiation decreased dramatically the mechanical parameters of enamel and dentine. In non-irradiated teeth, demineralization had nearly the same effects of irradiation on the mechanical properties. In irradiated teeth, the effects of demineralization were negligible in comparison to non-irradiated teeth. Remineralization with Bifluorid12 {sup registered} or elmex gelee {sup registered} led to a partial improvement of the mechanical properties of the teeth. The enamel was more positively affected, by remineralization than the dentine. (orig.)

  9. Characterization of Ninjurin and TSC22 induction after X-irradiation of normal human skin cells

    International Nuclear Information System (INIS)

    Koike, Manabu; Ninomiya, Yasuharu; Koike, Aki

    2008-01-01

    The skin is an external organ that is most frequently exposed to radiation. It is important to elucidate the influence of radiation exposure on the skin at the molecular level. To identify radiation-responsive genes in human skin cells, we used microarray technology to examine the effects of irradiation on 641 genes in normal human epidermal keratinocytes at 4 h and 8 h postirradiation with a cytotoxic dose of X-ray (10 Gy). We found that 18 genes were upregulated and 35 genes were downregulated in keratinocytes at 4 h and/or 8 h postirradiation. Ninjurin, whose function remains unknown in keratinocytes, was induced most strongly by X-irradiation. Several known apoptosis-related genes, such as TSC22, were also upregulated. We characterized Ninjurin and TSC22 induction after X-irradiation of normal human skin cells. The induction of the expression of Ninjurin and TSC22 mRNA in keratinocytes following high-dose X-irradiation was confirmed by northern blot analysis. In dermal fibroblasts, Ninjurin, but not TSC22, was induced after X-ray irradiation. The dependence of both gene expression on the status of an apoptosis regulator, p53, was found. In addition, the expression of both mRNA was induced upon treatment with an apoptosis inducer, etoposide. On the other hand, TSC22, but not Ninjurin, was induced and accumulated in keratinocytes upon treatment with an apoptosis inducer, anisomycin. However, in transient expression assay, EYFP-TSC22, as well as EYFP-Ninjurin or EYFP alone, did not induce apoptosis in keratinocytes in contrast to EYFP-GADD45. Taken together, these findings have important implications on the understanding of the mechanism underlying the complex response of skin cells following X-irradiation. (author)

  10. The Elemental Composition of Normal and Irradiated Rice Moth Corcyra Cephalonica (Staint) (Lepidoptera-Pyralidae)

    International Nuclear Information System (INIS)

    Abassy, S.A.

    2012-01-01

    The objective of this study was to determine the variation induced in the elemental composition of the total body tissue of corcyra cephalonica Adult males and females wear irradiated as adult with 50,150 and 250 Gy or as, 5 days old egg with 25 Gy and 5 days old pupae with 50 Gy .The result obtained showed that phosphorus was the highest concentrated element in males but in case of female, potassium was the most abundant element. We notice that the arrangement of the ten elements was changed as a result of irradiation. In general, there was a slight difference in elemental composition between sexes in irradiated adults and immature stages. The effect of gamma irradiation was extended from 5 days old eggs to adults. The results indicated that adults emerged from irradiated 5 days old eggs were more sensitive than older one. The difference was always dose dependent. Radiation dis infestations method could be used for the control of insects. It is safer than other means of control and, the minimal required dose does not cause undesirable changes

  11. Cell kinetical aspect of normal tissue damages in relation to radiosensitivity of cells, especially from the points of LQ model

    International Nuclear Information System (INIS)

    Tsubouchi, Susumu; Oohara, Hiroshi.

    1989-01-01

    Several points on the early and late radiation induced-normal tissue damages in terms of LQ model in multifractionation experiments of isoeffect were discussed from two fractors, (1) dose-responses of cell survivals or of tissue damages and (2) principles of the model. Application of the model to the both early and late tissue damages was fairly difficult in several tissues and several experimental conditions. In early damages, cell survival curve of single irradiation did not always fit to LQ model and further more incomlete repair as well as repopulation in multifractionation experiment contradicted the model especially in low dose fractionation. In late damages, the damages themselves did not express directly cell survival but probably indicate the degree of functional cell damage at the level of 10 -1 . As most isoeffects in early damages were taken at the level of 10 -3 , the comparison of two results from early and late tissue damages indicated the lack of coordinations both conceptionally and experimentally. (author)

  12. Survival of human osteosarcoma cells and normal human fibroblasts following alpha particle irradiation

    International Nuclear Information System (INIS)

    Lloyd, E.L.; Gemmell, M.A.

    1981-01-01

    Cell survival of human osteosarcoma cells in culture following alpha particle irradiation is reported here for the first time. The osteosarcoma cell line (TE-85) is found to be less sensitive to inactivation by 5.6 MeV alpha particles (LET 86 keV/μm) than normal diploid human fibroblasts (NFS). Values for the mean lethal doses were estimated to be 103 rads for the TE-85 cells compared with 68 rads for the NFS cultures irradiated under identical conditions. It is postulated that the aneuploidy of the tumor cells with increased DNA chromosomal material may confer a selective advantage for the survival of tumor cells relative to normal cells with diploid chromosomes

  13. A combination of HARMONIE short time direct normal irradiance forecasts and machine learning: The #hashtdim procedure

    Science.gov (United States)

    Gastón, Martín; Fernández-Peruchena, Carlos; Körnich, Heiner; Landelius, Tomas

    2017-06-01

    The present work describes the first approach of a new procedure to forecast Direct Normal Irradiance (DNI): the #hashtdim that treats to combine ground information and Numerical Weather Predictions. The system is centered in generate predictions for the very short time. It combines the outputs from the Numerical Weather Prediction Model HARMONIE with an adaptive methodology based on Machine Learning. The DNI predictions are generated with 15-minute and hourly temporal resolutions and presents 3-hourly updates. Each update offers forecasts to the next 12 hours, the first nine hours are generated with 15-minute temporal resolution meanwhile the last three hours present hourly temporal resolution. The system is proved over a Spanish emplacement with BSRN operative station in south of Spain (PSA station). The #hashtdim has been implemented in the framework of the Direct Normal Irradiance Nowcasting methods for optimized operation of concentrating solar technologies (DNICast) project, under the European Union's Seventh Programme for research, technological development and demonstration framework.

  14. Determination and correlation of spatial distribution of trace elements in normal and neoplastic breast tissues evaluated by μ-XRF

    International Nuclear Information System (INIS)

    Silva, M.P.; Oliveira, M.A.; Poletti, M.E.

    2012-01-01

    Full text: Some trace elements, naturally present in breast tissues, participate in a large number of biological processes, which include among others, activation or inhibition of enzymatic reactions and changes on cell membranes permeability, suggesting that these elements may influence carcinogenic processes. Thus, knowledge of the amounts of these elements and their spatial distribution in normal and neoplastic tissues may help in understanding the role of these elements in the carcinogenic process and tumor progression of breast cancers. Concentrations of trace elements like Ca, Fe, Cu and Zn, previously studied at LNLS using TXRF and conventional XRF, were elevated in neoplastic breast tissues compared to normal tissues. In this study we determined the spatial distribution of these elements in normal and neoplastic breast tissues using μ-XRF technique. We analyzed 22 samples of normal and neoplastic breast tissues (malignant and benign) obtained from paraffin blocks available for study at the Department of Pathology HC-FMRP/USP. From the blocks, a small fraction of material was removed and subjected to histological sections of 60 μm thick made with a microtome. The slices where placed in holder samples and covered with ultralen film. Tissue samples were irradiated with a white beam of synchrotron radiation. The samples were positioned at 45 degrees with respect to the incident beam on a table with 3 freedom degrees (x, y and z), allowing independent positioning of the sample in these directions. The white beam was collimated by a 20 μm microcapillary and samples were fully scanned. At each step, a spectrum was detected for 10 s. The fluorescence emitted by elements present in the sample was detected by a Si (Li) detector with 165 eV at 5.9 keV energy resolution, placed at 90 deg with respect to the incident beam. Results reveal that trace elements Ca-Zn and Fe-Cu could to be correlated in malignant breast tissues. Quantitative results, achieved by Spearman

  15. Effects of hyperthermia and X-irradiation on mouse stromal tissue

    International Nuclear Information System (INIS)

    Wondergem, J.; Haveman, J.

    1986-01-01

    The sensitivity of normal stroma to heat, irradiation and heat combined with irradiation, was studied using the tumour bed effect (TBE) assay. Irradiation before implantation led to a TBE, dose dependent below 15 Gy, but remaining relatively constant above. The interval (0-90 days) between irradiation and tumour implantation did not influence the magnitude of the TBE. Hyperthermia with large heat doses (45-60 min at 44 0 C) before implantation may lead to a TBE. The interval between hyperthermia and tumour implantation was very important. Results showed that the recovery from heat-induced stromal damage is very rapid. When the interval between hyperthermia and tumour implantation was 10 days or longer, no TBE could be observed. Irradiation combined with large heat doses (30-60 min at 44 0 C) decreased the radiation-induced TBE. The combination of irradiation with mild heat treatments (15 min at 44 0 C) could lead to a larger TBE then after irradiation alone. When hyperthermia was given prior to irradiation, the interval between heat and irradiation proved to be very important. With large intervals (21 days or longer), TBE values were about the same as with irradiation alone. When heat was given after irradiation, irradiation-induced TBE was always reduced. (UK)

  16. Glycogen accumulation in normal and irradiated minced muscle autografts on frog gastrocnemius

    International Nuclear Information System (INIS)

    Malhotra, R.K.; Kaul, R.; Malhotra, N.

    1989-01-01

    Alterations induced in glycogen content and phosphorylase activity have been studied in normal and irradiated minced muscle autografts on frog gastrocnemius at days 1, 3, 5, 7, 10, 15 and 30 postgrafting. The changes observed in the glycogen content and phosphorylase activity conform to the degeneration and regeneration phases of muscle repair. An attempt has been made to explain the altered glycogen utilizing capacities of the frog skeletal muscle during its repair and regeneration. (author)

  17. Effect of irradiation on the periodontal tissues in streptozotocin-induced diabetic rats

    International Nuclear Information System (INIS)

    Park, Dong Sin; Hwang, Eui Hwan; Lee, Sang Rae

    2005-01-01

    To observe the histopathological changes in the periodontal tissues of mandibular molars in streptozotocin-induced diabetic rats after irradiation. The male Sprague-Dawley rats weighing approximately 250 gm were divided into four groups; control, diabetes, irradiation, and diabetes - irradiation groups. Diabetes mellitus was induced in the rats by injecting streptozotocin. Rats in the control and irradiation groups were injected with citrate buffer only. After 5 days, the head and neck region of the rats in irradiation and diabetes - irradiation groups were irradiated with a single absorbed dose of 10 Gy. All the rats were sacrificed at 3, 7, 14, 21, and 28 days after irradiation. The specimen including the mandibular molars were sectioned and observed using a histopathological method. In the diabetes group, osteoclastic activity was observed in the alveolar bone and the root throughout the period of experiment. Also, osteoblastic and fibroblastic activities were markedly decreased. In the irradiation group, the osteoclasts were observed in the alveolar bone and the dilated capillaries were increased in the early experimental phases. However, vigorous osteoblastic activity was noted in the late experimental phases. In the diabetes- irradiation group, osteoblastic activity in the alveolar bone and the root was observed in the early experimental phases. However, there were no resorption and osteoblastic activity in the alveolar bone and the root in the late experimental phases, and obvious atrophic change of fibrous tissues was noted. This experiment suggests that osteoblastic activity was caused by irradiation in the late experimental phases, but atrophic change of the periodontal ligament tissues was induced after irradiation in diabetic state.

  18. Natural pregnancy and normal delivery after intracapsular irradiation for symptomatic craniopharyngioma

    International Nuclear Information System (INIS)

    Kodama, Takafumi; Matsukado, Yasuhiko; Miura, Masaki; Takada, Akira

    1986-01-01

    Treatment for craniopharyngioma, particularly in adults and cases of recurrence, is still fraught with problems. One difficulty is that postoperative hormonal function may be abnormal even after successful surgery. We have treated craniopharyngioma primarily with simple evacuation and intracapsular irradiation, using 198 Au-colloid. Only a few cases of natural pregnancy and normal delivery following treatment for craniopharyngioma with hypothalamic extension have been reported. We will describe and discuss a case in which natural pregnancy and normal delivery occurred twice after such treatment. (author)

  19. Palatal shelf epithelium: a morphologic and histochemical study in X-irradiated and normal mice

    International Nuclear Information System (INIS)

    Gartner, L.P.; Hiatt, J.L.; Provenza, D.V.

    1978-01-01

    The palatal shelf epithelium of normal and irradiated mice was examined morphologically and histochemically, utilizing the periodic acid-Schiff (PAS) technique for the demonstration of the basement membrane and the Nitro BT method for succinate dehydrogenase activity in order to demonstrate the metabolic competence of its cells. The 'programmed cell death theory' was not supported by the present investigation, since the cells of the medial ridge epithelium retained their structural and metabolic integrity even subsequent to the formation of cell nests. Additionally, the medial ridge epithelium of mice with radiation-induced cleft palates demonstrated normal structural and metabolic integrity long past the prospective time of fusion. (author)

  20. Natural pregnancy and normal delivery after intracapsular irradiation for symptomatic craniopharyngioma. Case report

    Energy Technology Data Exchange (ETDEWEB)

    Kodama, Takafumi; Matsukado, Yasuhiko; Miura, Masaki; Takada, Akira

    1986-01-01

    Treatment for craniopharyngioma, particularly in adults and cases of recurrence, is still fraught with problems. One difficulty is that postoperative hormonal function may be abnormal even after successful surgery. We have treated craniopharyngioma primarily with simple evacuation and intracapsular irradiation, using /sup 198/Au-colloid. Only a few cases of natural pregnancy and normal delivery following treatment for craniopharyngioma with hypothalamic extension have been reported. We will describe and discuss a case in which natural pregnancy and normal delivery occurred twice after such treatment.

  1. Radioprotection by WR-151327 against the late normal tissue damage in mouse hind legs from gamma ray radiation

    International Nuclear Information System (INIS)

    Matsushita, Satoru; Ando, Koichi; Koike, Sachiko

    1994-01-01

    To evaluate the protective effect of WR-151327 on late radiation-induced damaged to normal tissues in mice, the right hind legs of mice with or without WR-151327 administration (400 mg/kg) were irradiated with 137 Cs gamma rays. Leg contracture and skin shrinkage assays were performed at 380 days after irradiation. The mice were killed on day 400 postirradiation and histological sections of the legs were made. The thickness of the dermis, epidermis, and skin (dermis plus epidermis) was measured. The muscular area of the legs and the posterior knee angle between the femur and tibia were also measured. The left hind legs were similarly assessed as nonirradiated controls. Group means and standard deviations were calculated and dose-response curves were drawn for every endpoint. Then, the dose modifying factor (DMF) for each endpoint and the correlations among endpoints were determined. Latae damage assayed by leg contracture and skin shrinkage progressed with increasing radiation dose. However, it was reduced by drug treatment. The significant effect was indicated for skin shrinkage by a DMF of 1.8 at 35%. The DMF for leg contracture was 1.3 at 6 mm. In the irradiated legs, epidermal hyperplasia and dermal fibrosis in the skin, muscular atrophy, and extension disturbance of the knee joint were observed. These changes progressed with increasing radiation dose. Skin damage assayed by the present endpoints was also reduced by drug treatment by DMFs of 1.4 to 1.7. However, DMFs for damage to the muscle and knee were not determined because no isoeffect was observed. There were good correlations between leg contracture or skin shrinkage and the other endpoints in both untreated and drug-treated mice. WR-151327 has the potential to protect against radiation-induced late normal tissue damage. 17 refs., 6 figs., 2 tabs

  2. Active specific immunotherapy using the immune reaction of a low-dose irradiated tumor tissue

    International Nuclear Information System (INIS)

    Ogawa, Y.; Imanaka, K.; Ashida, C.; Takashima, H.; Imajo, Y.; Kimura, S.

    1983-01-01

    Active specific immunotherapy using the immune reaction of a low-dose irradiated tumor tissue was studied on the transplanted MM46 tumor of female C3H/He mice after radiotherapy. MM46 tumor cells were inoculated into the right hind paws of mice. On the 5th day, irradiation with the dose irradiated tumor tissue (2000 rad on the fifth day), were injected into the left hind paws of the tumor-bearing mice. Effectiveness of this active specific immunotherapy against tumor was evaluated by the regression of tumor and survival rate of mice. Tumor was markedly regressed and survival rate was significantly increased by the active specific immunitherapy

  3. Radiobiology of normal tissue. Scientific advances and perspectives; Strahlenbiologie der Normalgewebe. Wissenschaftliche Fortschritte und Perspektiven

    Energy Technology Data Exchange (ETDEWEB)

    Doerr, W. [Medizinische Univ. Wien (Austria). Universitaetsklinik fuer Strahlentherapie; Medizinische Univ. Wien (Austria). Universitaetsklinik fuer Radioonkologie; Medizinische Univ. Wien (Austria). Christian Doppler Labor fuer Medizinische Strahlenforschung fuer die Radioonkologie; Herskind, C. [Universitaetsmedizin Mannheim, Heidelberg Univ., Mannheim (Germany). Labor fuer Zellulaere und Molekulare Radioonkologie

    2012-11-15

    Radiotherapy involves always the exposure of normal tissue, resulting in an excepted risk of complications. The side effect rate is therefore the compromise between optimized tumor doses and the side effect minimization. The report covers the issues target cell hypothesis and the consequences, new aspect of the pathogenesis of normal issue reactions and strategies of targeted reduction of normal tissue effects. The complexity of the radiobiological processes, the specificity and action mechanisms, the mutual interactions of chemical and radiological processes require further coordinated radiobiological research in the future.

  4. Radiotherapy- and chemotherapy-induced normal tissue damage. The role of cytokines and adhesion molecules

    International Nuclear Information System (INIS)

    Plevova, P.

    2002-01-01

    Background. Ionising radiation and cytostatic agents used in cancer therapy exert damaging effects on normal tissues and induce a complex response at the cellular and molecular levels. Cytokines and adhesion molecules are involved in this response. Methods. Published data on the given topic have been reviewed. Results and conclusions. Various cytokines and adhesion molecules, including tumor necrosis factor α, interleukins- 1,-2,-4, and -6, interferon γ, granulocyte macrophage- and macrophage- colony stimulating factors, transforming growth factor β, platelet-derived growth factor, insulin-like growth factor I, fibroblast and epidermal growth factors, platelet-activating factor, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, E- and P-selectins are involved in the response of normal tissues to ionizing radiation- and chemotherapy- induced normal tissues damage and are co-responsible for some side effects of these treatment modalities, including fever, anorexia and fatigue, suppression of hematopoiesis, both acute and late local tissue response. (author)

  5. An Experimental Study on the Effects of Co-60 Irradiation on the Rat Tongue Tissue

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Seon Kee; Lee, Sang Rae [Dept. of Oral Radiology, College of Dentistry, Kyung Hee University, Seoul (Korea, Republic of)

    1990-02-15

    It is known that radiation therapy is a kind of treatment choices of the maxillofacial tumors. This study is designed to investigate the effects of irradiation on rat's tongue tissues as functional tissues which relate to taste, mastication, and pronunciation. 88 rats (Sprague Dawley branch, male) were divided into control group of 4 and experimental group of 84. Experimental group was singly exposed to Co-60 irradiation with 8, 13, 18 Gy in the head and neck region. Animals were sacrificed on 1 hour, 3 hours, 6 hours, 1 day, 3 days, 7 days, and 28 days after the irradiation. The specimens were observed by histopathological examination employing H-E stain and Van-Gieson stain. The results were follows; 1. The tongue tissue were severely swollen on the 1 hour after irradiation, but gradually decreased in course of time. 2. The basal cells of epithelium of tongue proliferated at initial stage of irradiation, but gradually decreased. The Keratin layer were gradually increased. 4. The tissue changes after irradiation were gradually increased by the degree of irradiation.

  6. Chronic irradiation of gonad tissue of the male rat

    International Nuclear Information System (INIS)

    Lemaire, G.; Maas, J.

    1982-01-01

    The effects of chronically irradiating rats' testes with daily gamma radiation doses of (1.4 - 8.6) x 10 -2 Gy for 71-140 days were studied. After about 30 days irradiation, the testes weights decrease and level off at about 75 days. Irradiation also caused the germ cells in the seminiferous tubules to disappear progressively, completely when the dose exceeded 6 x 10 -2 Gy/day and partially with the lower doses. At doses below 6 x 10 -2 Gy/day, there was also a delay in the spermatogenesis cycle with the spermatogonia and spermatocytes appearing to reach a new equilibrium, the level of which depended on the dose. (U.K.)

  7. MRI characterization of brown adipose tissue in obese and normal-weight children

    Energy Technology Data Exchange (ETDEWEB)

    Deng, Jie; Rigsby, Cynthia K.; Shore, Richard M. [Ann and Robert H. Lurie Children' s Hospital of Chicago, Department of Medical Imaging, 225 E. Chicago Ave., Box 9, Chicago, IL (United States); Northwestern University, Department of Radiology, Feinberg School of Medicine, Chicago, IL (United States); Schoeneman, Samantha E. [Ann and Robert H. Lurie Children' s Hospital of Chicago, Department of Medical Imaging, 225 E. Chicago Ave., Box 9, Chicago, IL (United States); Zhang, Huiyuan [John H. Stroger, Jr. Hospital of Cook County, Collaborative Research Unit, Chicago, IL (United States); Kwon, Soyang [Ann and Robert H. Lurie Children' s Hospital of Chicago, Stanley Manne Children' s Research Institute, Chicago, IL (United States); Northwestern University, Department of Pediatrics, Feinberg School of Medicine, Chicago, IL (United States); Josefson, Jami L. [Ann and Robert H. Lurie Children' s Hospital of Chicago, Division of Endocrinology, Chicago, IL (United States); Northwestern University, Department of Pediatrics, Feinberg School of Medicine, Chicago, IL (United States)

    2015-10-15

    Brown adipose tissue (BAT) is identified in mammals as an adaptive thermogenic organ for modulation of energy expenditure and heat generation. Human BAT may be primarily composed of brown-in-white (BRITE) adipocytes and stimulation of BRITE may serve as a potential target for obesity interventions. Current imaging studies of BAT detection and characterization have been mainly limited to PET/CT. MRI is an emerging application for BAT characterization in healthy children. To exploit Dixon and diffusion-weighted MRI methods to characterize cervical-supraclavicular BAT/BRITE properties in normal-weight and obese children while accounting for pubertal status. Twenty-eight healthy children (9-15 years old) with a normal or obese body mass index participated. MRI exams were performed to characterize supraclavicular adipose tissues by measuring tissue fat percentage, T2*, tissue water mobility, and microvasculature properties. We used multivariate linear regression models to compare tissue properties between normal-weight and obese groups while accounting for pubertal status. MRI measurements of BAT/BRITE tissues in obese children showed higher fat percentage (P < 0.0001), higher T2* (P < 0.0001), and lower diffusion coefficient (P = 0.015) compared with normal-weight children. Pubertal status was a significant covariate for the T2* measurement, with higher T2* (P = 0.0087) in pubertal children compared to prepubertal children. Perfusion measurements varied by pubertal status. Compared to normal-weight children, obese prepubertal children had lower perfusion fraction (P = 0.003) and pseudo-perfusion coefficient (P = 0.048); however, obese pubertal children had higher perfusion fraction (P = 0.02) and pseudo-perfusion coefficient (P = 0.028). This study utilized chemical-shift Dixon MRI and diffusion-weighted MRI methods to characterize supraclavicular BAT/BRITE tissue properties. The multi-parametric evaluation revealed evidence of morphological differences in brown

  8. MRI characterization of brown adipose tissue in obese and normal-weight children

    International Nuclear Information System (INIS)

    Deng, Jie; Rigsby, Cynthia K.; Shore, Richard M.; Schoeneman, Samantha E.; Zhang, Huiyuan; Kwon, Soyang; Josefson, Jami L.

    2015-01-01

    Brown adipose tissue (BAT) is identified in mammals as an adaptive thermogenic organ for modulation of energy expenditure and heat generation. Human BAT may be primarily composed of brown-in-white (BRITE) adipocytes and stimulation of BRITE may serve as a potential target for obesity interventions. Current imaging studies of BAT detection and characterization have been mainly limited to PET/CT. MRI is an emerging application for BAT characterization in healthy children. To exploit Dixon and diffusion-weighted MRI methods to characterize cervical-supraclavicular BAT/BRITE properties in normal-weight and obese children while accounting for pubertal status. Twenty-eight healthy children (9-15 years old) with a normal or obese body mass index participated. MRI exams were performed to characterize supraclavicular adipose tissues by measuring tissue fat percentage, T2*, tissue water mobility, and microvasculature properties. We used multivariate linear regression models to compare tissue properties between normal-weight and obese groups while accounting for pubertal status. MRI measurements of BAT/BRITE tissues in obese children showed higher fat percentage (P < 0.0001), higher T2* (P < 0.0001), and lower diffusion coefficient (P = 0.015) compared with normal-weight children. Pubertal status was a significant covariate for the T2* measurement, with higher T2* (P = 0.0087) in pubertal children compared to prepubertal children. Perfusion measurements varied by pubertal status. Compared to normal-weight children, obese prepubertal children had lower perfusion fraction (P = 0.003) and pseudo-perfusion coefficient (P = 0.048); however, obese pubertal children had higher perfusion fraction (P = 0.02) and pseudo-perfusion coefficient (P = 0.028). This study utilized chemical-shift Dixon MRI and diffusion-weighted MRI methods to characterize supraclavicular BAT/BRITE tissue properties. The multi-parametric evaluation revealed evidence of morphological differences in brown

  9. Differential expression of GPR30 in preeclampsia placenta tissue and normal placenta tissue and its clinical significance

    Directory of Open Access Journals (Sweden)

    Ben-Zhou Feng

    2016-04-01

    Full Text Available Objective: To study the differential expression of GPR30 in preeclampsia placenta tissue and normal placenta tissue and its clinical significance. Methods: Preeclampsia placenta tissue and normal placenta tissue were collected and GPR30 expression levels were detected; human umbilical vein endothelial cells were cultured and processed with GRP30 inhibitor and GRP30 agonist combined with hypoxia-reoxygenation respectively, and cell apoptosis as well as pro-angiogenesis molecule and apoptosis molecule contents were detected. Results: mRNA content and protein content of GRP30 in preeclampsia placenta tissue were significantly lower than those in normal placenta tissue; apoptosis rate of G15 group was significantly higher than that of control group, VEGF and bFGF contents in supernatant were significantly lower than those of control group, and mRNA contents of Bax, Caspase-3 and Caspase-9 in cells were significantly higher than those of control group; apoptosis rate of H/R group was significantly higher than that of control group, VEGF and bFGF contents in supernatant were significantly lower than those of control group, and mRNA contents of Bax, Caspase-3 and Caspase-9 in cells were significantly higher than those of control group; apoptosis rate of G1 group was significantly lower than that of H/R group, VEGF and bFGF contents in supernatant were significantly higher than those of H/R group, and mRNA contents of Bax, Caspase-3 and Caspase-9 in cells were significantly lower than those of H/R group. Conclusions: Low expression of GPR30 in placenta tissue is closely associated with the occurrence of preeclampsia, enhancing GPR function can reduce endothelial cell apoptosis and increase the contents of pro-angiogenesis factors, and it has endothelial protection effect.

  10. Multivariate Normal Tissue Complication Probability Modeling of Heart Valve Dysfunction in Hodgkin Lymphoma Survivors

    International Nuclear Information System (INIS)

    Cella, Laura; Liuzzi, Raffaele; Conson, Manuel; D’Avino, Vittoria; Salvatore, Marco; Pacelli, Roberto

    2013-01-01

    Purpose: To establish a multivariate normal tissue complication probability (NTCP) model for radiation-induced asymptomatic heart valvular defects (RVD). Methods and Materials: Fifty-six patients treated with sequential chemoradiation therapy for Hodgkin lymphoma (HL) were retrospectively reviewed for RVD events. Clinical information along with whole heart, cardiac chambers, and lung dose distribution parameters was collected, and the correlations to RVD were analyzed by means of Spearman's rank correlation coefficient (Rs). For the selection of the model order and parameters for NTCP modeling, a multivariate logistic regression method using resampling techniques (bootstrapping) was applied. Model performance was evaluated using the area under the receiver operating characteristic curve (AUC). Results: When we analyzed the whole heart, a 3-variable NTCP model including the maximum dose, whole heart volume, and lung volume was shown to be the optimal predictive model for RVD (Rs = 0.573, P<.001, AUC = 0.83). When we analyzed the cardiac chambers individually, for the left atrium and for the left ventricle, an NTCP model based on 3 variables including the percentage volume exceeding 30 Gy (V30), cardiac chamber volume, and lung volume was selected as the most predictive model (Rs = 0.539, P<.001, AUC = 0.83; and Rs = 0.557, P<.001, AUC = 0.82, respectively). The NTCP values increase as heart maximum dose or cardiac chambers V30 increase. They also increase with larger volumes of the heart or cardiac chambers and decrease when lung volume is larger. Conclusions: We propose logistic NTCP models for RVD considering not only heart irradiation dose but also the combined effects of lung and heart volumes. Our study establishes the statistical evidence of the indirect effect of lung size on radio-induced heart toxicity

  11. Mechanistic simulation of normal-tissue damage in radiotherapy-implications for dose-volume analyses

    International Nuclear Information System (INIS)

    Rutkowska, Eva; Baker, Colin; Nahum, Alan

    2010-01-01

    A radiobiologically based 3D model of normal tissue has been developed in which complications are generated when 'irradiated'. The aim is to provide insight into the connection between dose-distribution characteristics, different organ architectures and complication rates beyond that obtainable with simple DVH-based analytical NTCP models. In this model the organ consists of a large number of functional subunits (FSUs), populated by stem cells which are killed according to the LQ model. A complication is triggered if the density of FSUs in any 'critical functioning volume' (CFV) falls below some threshold. The (fractional) CFV determines the organ architecture and can be varied continuously from small (series-like behaviour) to large (parallel-like). A key feature of the model is its ability to account for the spatial dependence of dose distributions. Simulations were carried out to investigate correlations between dose-volume parameters and the incidence of 'complications' using different pseudo-clinical dose distributions. Correlations between dose-volume parameters and outcome depended on characteristics of the dose distributions and on organ architecture. As anticipated, the mean dose and V 20 correlated most strongly with outcome for a parallel organ, and the maximum dose for a serial organ. Interestingly better correlation was obtained between the 3D computer model and the LKB model with dose distributions typical for serial organs than with those typical for parallel organs. This work links the results of dose-volume analyses to dataset characteristics typical for serial and parallel organs and it may help investigators interpret the results from clinical studies.

  12. β class II tubulin predominates in normal and tumor breast tissues

    International Nuclear Information System (INIS)

    Dozier, James H; Hiser, Laree; Davis, Jennifer A; Thomas, Nancy Stubbs; Tucci, Michelle A; Benghuzzi, Hamed A; Frankfurter, Anthony; Correia, John J; Lobert, Sharon

    2003-01-01

    Antimitotic chemotherapeutic agents target tubulin, the major protein in mitotic spindles. Tubulin isotype composition is thought to be both diagnostic of tumor progression and a determinant of the cellular response to chemotherapy. This implies that there is a difference in isotype composition between normal and tumor tissues. To determine whether such a difference occurs in breast tissues, total tubulin was fractionated from lysates of paired normal and tumor breast tissues, and the amounts of β-tubulin classes I + IV, II, and III were measured by competitive enzyme-linked immunosorbent assay (ELISA). Only primary tumor tissues, before chemotherapy, were examined. Her2/neu protein amplification occurs in about 30% of breast tumors and is considered a marker for poor prognosis. To gain insight into whether tubulin isotype levels might be correlated with prognosis, ELISAs were used to quantify Her2/neu protein levels in these tissues. β-Tubulin isotype distributions in normal and tumor breast tissues were similar. The most abundant β-tubulin isotypes in these tissues were β-tubulin classes II and I + IV. Her2/neu levels in tumor tissues were 5–30-fold those in normal tissues, although there was no correlation between the Her2/neu biomarker and tubulin isotype levels. These results suggest that tubulin isotype levels, alone or in combination with Her2/neu protein levels, might not be diagnostic of tumorigenesis in breast cancer. However, the presence of a broad distribution of these tubulin isotypes (for example, 40–75% β-tubulin class II) in breast tissue, in conjunction with other factors, might still be relevant to disease progression and cellular response to antimitotic drugs

  13. DNA double-strand break repair of blood lymphocytes and normal tissues analysed in a preclinical mouse model: implications for radiosensitivity testing.

    Science.gov (United States)

    Rübe, Claudia E; Grudzenski, Saskia; Kühne, Martin; Dong, Xiaorong; Rief, Nicole; Löbrich, Markus; Rübe, Christian

    2008-10-15

    Radiotherapy is an effective cancer treatment, but a few patients suffer severe radiation toxicities in neighboring normal tissues. There is increasing evidence that the variable susceptibility to radiation toxicities is caused by the individual genetic predisposition, by subtle mutations, or polymorphisms in genes involved in cellular responses to ionizing radiation. Double-strand breaks (DSB) are the most deleterious form of radiation-induced DNA damage, and DSB repair deficiencies lead to pronounced radiosensitivity. Using a preclinical mouse model, the highly sensitive gammaH2AX-foci approach was tested to verify even subtle, genetically determined DSB repair deficiencies known to be associated with increased normal tissue radiosensitivity. By enumerating gammaH2AX-foci in blood lymphocytes and normal tissues (brain, lung, heart, and intestine), the induction and repair of DSBs after irradiation with therapeutic doses (0.1-2 Gy) was investigated in repair-proficient and repair-deficient mouse strains in vivo and blood samples irradiated ex vivo. gammaH2AX-foci analysis allowed to verify the different DSB repair deficiencies; even slight impairments caused by single polymorphisms were detected similarly in both blood lymphocytes and solid tissues, indicating that DSB repair measured in lymphocytes is valid for different and complex organs. Moreover, gammaH2AX-foci analysis of blood samples irradiated ex vivo was found to reflect repair kinetics measured in vivo and, thus, give reliable information about the individual DSB repair capacity. gammaH2AX analysis of blood and tissue samples allows to detect even minor genetically defined DSB repair deficiencies, affecting normal tissue radiosensitivity. Future studies will have to evaluate the clinical potential to identify patients more susceptible to radiation toxicities before radiotherapy.

  14. Study on changes of sperm count and testis tissue in black mouse after neutron irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Chun, Ki Jung; Seo, Won Sook [KAERI, Daejeon (Korea, Republic of); Son, Hwa Young [Chungnam National Univ., Daejeon (Korea, Republic of)

    2006-03-15

    For the purpose of the biological effect in black mouse by neutron irradiation, mice were irradiated with 16 or 32 Gy neutron (flux: 1.036739E+09) by lying flat pose at BNCT facility on HANARO Reactors. And 90 days later of irradiation, physical changes of testis and testis tissue were examined. There were no weight changes but a little bit volume changes and sperm counts in the tests. Atrophy of seminiferous tubules irradiated with 32 Gy neutron is increased in number and severity and those in stage VI showed depletion of spermatogonia and pachytene spermatocytes compared to the non-irradiated control group. Testis damage of black mouse was not recovered after long time by 32 Gy neutron irradiation.

  15. Study on changes of sperm count and testis tissue in black mouse after neutron irradiation

    International Nuclear Information System (INIS)

    Chun, Ki Jung; Seo, Won Sook; Son, Hwa Young

    2006-01-01

    For the purpose of the biological effect in black mouse by neutron irradiation, mice were irradiated with 16 or 32 Gy neutron (flux: 1.036739E+09) by lying flat pose at BNCT facility on HANARO Reactors. And 90 days later of irradiation, physical changes of testis and testis tissue were examined. There were no weight changes but a little bit volume changes and sperm counts in the tests. Atrophy of seminiferous tubules irradiated with 32 Gy neutron is increased in number and severity and those in stage VI showed depletion of spermatogonia and pachytene spermatocytes compared to the non-irradiated control group. Testis damage of black mouse was not recovered after long time by 32 Gy neutron irradiation

  16. Influence of chronic internal and acute external irradiations on the critical tissues of plants

    International Nuclear Information System (INIS)

    Kostyuk, O.P.; Ryasnenko, N.A.; Grodzins'kij, D.M.

    1998-01-01

    Peculiarities of chronic internal and acute external irradiations of the critical (as for irradiation influence) plants part, meristem, are studied. In particular, the investigation has aimed to evaluate the level of doses, accumulated by plant tissues, of the chronic internal irradiation from radiocaesium incorporated by them, and to compare its possible effect to one caused by the acute external irradiation. It is shown that the effects of both chronic and acute irradiations have similar features, and it is assumed that they have the very same mechanisms. We think that such a parameter of the plant ability to accumulate radiocaesium as the ratio of its content in a root tip and in the whole root system is a very sensible and useful criterion to estimate the irradiation influence on plants

  17. The immune cell composition in Barrett's metaplastic tissue resembles that in normal duodenal tissue.

    Directory of Open Access Journals (Sweden)

    Alexandra Lind

    Full Text Available BACKGROUND AND OBJECTIVE: Barrett's esophagus (BE is characterized by the transition of squamous epithelium into columnar epithelium with intestinal metaplasia. The increased number and types of immune cells in BE have been indicated to be due to a Th2-type inflammatory process. We tested the alternative hypothesis that the abundance of T-cells in BE is caused by a homing mechanism that is found in the duodenum. PATIENTS AND METHODS: Biopsies from BE and duodenal tissue from 30 BE patients and duodenal tissue from 18 controls were characterized by immmunohistochemistry for the presence of T-cells and eosinophils(eos. Ex vivo expanded T-cells were further phenotyped by multicolor analysis using flowcytometry. RESULTS: The high percentage of CD4(+-T cells (69±3% (mean±SEM/n = 17, by flowcytometry, measured by flowcytometry and immunohistochemistry, and the presence of non-activated eosinophils found in BE by immunohistochemical staining, were not different from that found in duodenal tissue. Expanded lymphocytes from these tissues had a similar phenotype, characterized by a comparable but low percentage of αE(CD103 positive CD4(+cells (44±5% in BE, 43±4% in duodenum of BE and 34±7% in duodenum of controls and a similar percentage of granzyme-B(+CD8(+ cells(44±5% in BE, 33±6% in duodenum of BE and 36±7% in duodenum of controls. In addition, a similar percentage of α4β7(+ T-lymphocytes (63±5% in BE, 58±5% in duodenum of BE and 62±8% in duodenum of controls was found. Finally, mRNA expression of the ligand for α4β7, MAdCAM-1, was also similar in BE and duodenal tissue. No evidence for a Th2-response was found as almost no IL-4(+-T-cells were seen. CONCLUSION: The immune cell composition (lymphocytes and eosinophils and expression of intestinal adhesion molecule MAdCAM-1 is similar in BE and duodenum. This supports the hypothesis that homing of lymphocytes to BE tissue is mainly caused by intestinal homing signals rather than to an

  18. Distribution of Basement Membrane Molecules, Laminin and Collagen Type IV, in Normal and Degenerated Cartilage Tissues.

    Science.gov (United States)

    Foldager, Casper Bindzus; Toh, Wei Seong; Gomoll, Andreas H; Olsen, Bjørn Reino; Spector, Myron

    2014-04-01

    The objective of the present study was to investigate the presence and distribution of 2 basement membrane (BM) molecules, laminin and collagen type IV, in healthy and degenerative cartilage tissues. Normal and degenerated tissues were obtained from goats and humans, including articular knee cartilage, the intervertebral disc, and meniscus. Normal tissue was also obtained from patella-tibial enthesis in goats. Immunohistochemical analysis was performed using anti-laminin and anti-collagen type IV antibodies. Human and goat skin were used as positive controls. The percentage of cells displaying the pericellular presence of the protein was graded semiquantitatively. When present, laminin and collagen type IV were exclusively found in the pericellular matrix, and in a discrete layer on the articulating surface of normal articular cartilage. In normal articular (hyaline) cartilage in the human and goat, the proteins were found co-localized pericellularly. In contrast, in human osteoarthritic articular cartilage, collagen type IV but not laminin was found in the pericellular region. Nonpathological fibrocartilaginous tissues from the goat, including the menisci and the enthesis, were also positive for both laminin and collagen type IV pericellularly. In degenerated fibrocartilage, including intervertebral disc, as in degenerated hyaline cartilage only collagen type IV was found pericellularly around chondrocytes but with less intense staining than in non-degenerated tissue. In calcified cartilage, some cells were positive for laminin but not type IV collagen. We report differences in expression of the BM molecules, laminin and collagen type IV, in normal and degenerative cartilaginous tissues from adult humans and goats. In degenerative tissues laminin is depleted from the pericellular matrix before collagen type IV. The findings may inform future studies of the processes underlying cartilage degeneration and the functional roles of these 2 extracellular matrix proteins

  19. Distribution of Basement Membrane Molecules, Laminin and Collagen Type IV, in Normal and Degenerated Cartilage Tissues

    Science.gov (United States)

    Toh, Wei Seong; Gomoll, Andreas H.; Olsen, Bjørn Reino; Spector, Myron

    2014-01-01

    Objective: The objective of the present study was to investigate the presence and distribution of 2 basement membrane (BM) molecules, laminin and collagen type IV, in healthy and degenerative cartilage tissues. Design: Normal and degenerated tissues were obtained from goats and humans, including articular knee cartilage, the intervertebral disc, and meniscus. Normal tissue was also obtained from patella-tibial enthesis in goats. Immunohistochemical analysis was performed using anti-laminin and anti–collagen type IV antibodies. Human and goat skin were used as positive controls. The percentage of cells displaying the pericellular presence of the protein was graded semiquantitatively. Results: When present, laminin and collagen type IV were exclusively found in the pericellular matrix, and in a discrete layer on the articulating surface of normal articular cartilage. In normal articular (hyaline) cartilage in the human and goat, the proteins were found co-localized pericellularly. In contrast, in human osteoarthritic articular cartilage, collagen type IV but not laminin was found in the pericellular region. Nonpathological fibrocartilaginous tissues from the goat, including the menisci and the enthesis, were also positive for both laminin and collagen type IV pericellularly. In degenerated fibrocartilage, including intervertebral disc, as in degenerated hyaline cartilage only collagen type IV was found pericellularly around chondrocytes but with less intense staining than in non-degenerated tissue. In calcified cartilage, some cells were positive for laminin but not type IV collagen. Conclusions: We report differences in expression of the BM molecules, laminin and collagen type IV, in normal and degenerative cartilaginous tissues from adult humans and goats. In degenerative tissues laminin is depleted from the pericellular matrix before collagen type IV. The findings may inform future studies of the processes underlying cartilage degeneration and the functional

  20. Comparison of effective atomic numbers of the cancerous and normal kidney tissue

    International Nuclear Information System (INIS)

    Manjunatha, H.C.

    2015-01-01

    The effective atomic number (Z eff ) and electron density (N e ) of normal kidney and cancerous kidney have been computed for total and partial photon interactions by computing the molecular, atomic, and electronic cross section in the wide energy range of 1 keV-100 GeV using WinXCOM. The mean Z eff and N e of normal kidney and cancerous kidney in the various energy ranges and for total and partial photon interactions are tabulated. The variation of effective N e with energy is shown graphically for all photon interactions. In addition to this computer tomography (CT), numbers of normal kidney and cancerous kidney for photon interaction and energy absorption is also computed. The role of Z eff in the dual-energy dividing radiography is also discussed. The values of Z eff and N e for cancerous kidney are higher than normal kidney. This is due to the levels of elements K, Ca, Fe, Ni, and Se are lower and those of the elements Ti, Co, Zn, As, and Cd are higher in the cancer tissue of kidney than those observed in the normal tissue. The soft tissue and cancerous tissue are very similar, but their atomic number differs. The cancerous tissue exhibits a higher Z eff than the normal tissue. This fact helps in the dual-energy dividing radiography which enables to improve the diagnosis of the kidney cancer. Hence, the computed values may be useful in the diagnosis of the kidney cancer. CT numbers for normal kidney are higher than cancerous kidney. (author)

  1. Role of endothelium in radiation-induced normal tissue damages; Role de l'endothelium dans les dommages radio-induits aux tissus sains

    Energy Technology Data Exchange (ETDEWEB)

    Milliat, F

    2007-05-15

    More than half of cancers are treated with radiation therapy alone or in combination with surgery and/or chemotherapy. The goal of radiation therapy is to deliver enough ionising radiation to destroy cancer cells without exceeding the level that the surrounding healthy cells can tolerate. Unfortunately, radiation-induced normal tissue injury is still a dose limiting factor in the treatment of cancer with radiotherapy. The knowledge of normal tissue radiobiology is needed to determine molecular mechanisms involved in normal tissue pathogenic pathways in order to identify therapeutic targets and develop strategies to prevent and /or reduce side effects of radiation therapy. The endothelium is known to play a critical role in radiation-induced injury. Our work shows that endothelial cells promote vascular smooth muscle cell proliferation, migration and fibro-genic phenotype after irradiation. Moreover, we demonstrate for the first time the importance of PAI-1 in radiation-induced normal tissue damage suggesting that PAI-1 may represent a molecular target to limit injury following radiotherapy. We describe a new role for the TGF-b/Smad pathway in the pathogenesis of radiation-induced damages. TGF-b/Smad pathway is involved in the fibro-genic phenotype of VSMC induced by irradiated EC as well as in the radiation-induced PAI-1 expression in endothelial cells. (author)

  2. Role of endothelium in radiation-induced normal tissue damages; Role de l'endothelium dans les dommages radio-induits aux tissus sains

    Energy Technology Data Exchange (ETDEWEB)

    Milliat, F

    2007-05-15

    More than half of cancers are treated with radiation therapy alone or in combination with surgery and/or chemotherapy. The goal of radiation therapy is to deliver enough ionising radiation to destroy cancer cells without exceeding the level that the surrounding healthy cells can tolerate. Unfortunately, radiation-induced normal tissue injury is still a dose limiting factor in the treatment of cancer with radiotherapy. The knowledge of normal tissue radiobiology is needed to determine molecular mechanisms involved in normal tissue pathogenic pathways in order to identify therapeutic targets and develop strategies to prevent and /or reduce side effects of radiation therapy. The endothelium is known to play a critical role in radiation-induced injury. Our work shows that endothelial cells promote vascular smooth muscle cell proliferation, migration and fibro-genic phenotype after irradiation. Moreover, we demonstrate for the first time the importance of PAI-1 in radiation-induced normal tissue damage suggesting that PAI-1 may represent a molecular target to limit injury following radiotherapy. We describe a new role for the TGF-b/Smad pathway in the pathogenesis of radiation-induced damages. TGF-b/Smad pathway is involved in the fibro-genic phenotype of VSMC induced by irradiated EC as well as in the radiation-induced PAI-1 expression in endothelial cells. (author)

  3. The effect of irradiation on the subcutaneous fatty layer and the perirectal tissue by computed tomography

    International Nuclear Information System (INIS)

    Komatsu, Takashi

    1987-01-01

    Although it has been suggested that the subcutaneous fatty layer is affected by irradiation, the available reports have not been able to find out yet. While, it is reported that the intrapelvic fat increases in volume after whole pelvic irradiation. This paper report a study about the effect of irradiation on subcutaneous fatty layer and intrapelvic fat. The subjects studied were 20 cases treated by whole pelvic irradiation. The x-ray CT film was used to measure the subcutaneous fatty layer and the intrapelvic fat. Three slices, the lower end of sacro-iliac joint, upper end of the femoral head and upper rim of the pubic symphysis, were chosen as the cross section level, and the thickness of subcutaneous fatty layer on 6 points of the body and the presacral space (PS) were measured. Irradiation group was followed by measuring the thickness of fatty layer; before irradiation, 1 month, 3 or 4 months, 6 or 7 months and 12 months after irradiation. At the three of four points, which are included within the irradiation area, the thickness of subcutaneous fatty layer tended to increase after irradiation, though it showed increase or decrease at each period. This tendency was prominent at the lower than the upper slice of the pelvis. The other points, which are out of the irradiation field, showed no significant change and some of them even showed the tendency of decrease. Fatty layer of the presacral space tended to increase following irradiation, but there was no correlation with the irradiation dose. It is considered that the injury of subcutaneous tissue by irradiation results in the disturbance of blood flow and then it accelerates deposition of fat to the irradiated area. (author)

  4. Mechanisms of radiation-induced normal tissue toxicity and implications for future clinical trials

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jae Ho; Jenrow, Kenneth A.; Brown, Stephen L. [Dept.of Radiation Oncology, Henry Ford Health System, Detroit (United States)

    2014-09-15

    To summarize current knowledge regarding mechanisms of radiation-induced normal tissue injury and medical countermeasures available to reduce its severity. Advances in radiation delivery using megavoltage and intensity-modulated radiation therapy have permitted delivery of higher doses of radiation to well-defined tumor target tissues. Injury to critical normal tissues and organs, however, poses substantial risks in the curative treatment of cancers, especially when radiation is administered in combination with chemotherapy. The principal pathogenesis is initiated by depletion of tissue stem cells and progenitor cells and damage to vascular endothelial microvessels. Emerging concepts of radiation-induced normal tissue toxicity suggest that the recovery and repopulation of stromal stem cells remain chronically impaired by long-lived free radicals, reactive oxygen species, and pro-inflammatory cytokines/chemokines resulting in progressive damage after radiation exposure. Better understanding the mechanisms mediating interactions among excessive generation of reactive oxygen species, production of pro-inflammatory cytokines and activated macrophages, and role of bone marrow-derived progenitor and stem cells may provide novel insight on the pathogenesis of radiation-induced injury of tissues. Further understanding the molecular signaling pathways of cytokines and chemokines would reveal novel targets for protecting or mitigating radiation injury of tissues and organs.

  5. Mechanisms of radiation-induced normal tissue toxicity and implications for future clinical trials

    International Nuclear Information System (INIS)

    Kim, Jae Ho; Jenrow, Kenneth A.; Brown, Stephen L.

    2014-01-01

    To summarize current knowledge regarding mechanisms of radiation-induced normal tissue injury and medical countermeasures available to reduce its severity. Advances in radiation delivery using megavoltage and intensity-modulated radiation therapy have permitted delivery of higher doses of radiation to well-defined tumor target tissues. Injury to critical normal tissues and organs, however, poses substantial risks in the curative treatment of cancers, especially when radiation is administered in combination with chemotherapy. The principal pathogenesis is initiated by depletion of tissue stem cells and progenitor cells and damage to vascular endothelial microvessels. Emerging concepts of radiation-induced normal tissue toxicity suggest that the recovery and repopulation of stromal stem cells remain chronically impaired by long-lived free radicals, reactive oxygen species, and pro-inflammatory cytokines/chemokines resulting in progressive damage after radiation exposure. Better understanding the mechanisms mediating interactions among excessive generation of reactive oxygen species, production of pro-inflammatory cytokines and activated macrophages, and role of bone marrow-derived progenitor and stem cells may provide novel insight on the pathogenesis of radiation-induced injury of tissues. Further understanding the molecular signaling pathways of cytokines and chemokines would reveal novel targets for protecting or mitigating radiation injury of tissues and organs.

  6. Research progress in plant mutation by combining ion beam irradiations and tissue culture

    International Nuclear Information System (INIS)

    Zhou Linbin; Li Wenjian; Qu Ying; Li Ping

    2007-01-01

    About a new mutation breeding method which combines plant tissue culture technique with heavy ion beam irradiations were discussed in this paper with the principles, operation steps, molecular mechanisms, etc. The mutation method developed a few advantages coming from plant tissue culture, which can produce offspring by asexual ways. Meanwhile, using this method, the study of biological effects of high energy particles with different linear energy transfer values on plant tissues or cells can be explored and optimized in theory or practice. (authors)

  7. Leptin induction following irradiation is a conserved feature in mammalian epithelial cells and tissues.

    Science.gov (United States)

    Licursi, Valerio; Cestelli Guidi, Mariangela; Del Vecchio, Giorgia; Mannironi, Cecilia; Presutti, Carlo; Amendola, Roberto; Negri, Rodolfo

    2017-09-01

    Leptin (LEP) is a peptide hormone with multiple physiological functions. Besides its systemic actions, it has important peripheral roles such as a mitogen action on keratinocytes following skin lesions. We previously showed that LEP mRNA is significantly induced in response to neutron irradiation in mouse skin and that the protein increases in the irradiated epidermis and in the related subcutaneous adipose tissue. In this work, we investigated the post-transcriptional regulation of LEP by miRNAs and the conservation of LEP's role in radiation response in human cells. We used microarray analysis and real-time polymerase chain reaction (RT-PCR) to analyze modulation of miRNAs potentially targeting LEP in mouse skin following irradiation and bioinformatic analysis of transcriptome of irradiated human cell lines and cancer tissues from radiotherapy-treated patients to evaluate LEP expression. We show that a network of miRNAs potentially targeting LEP mRNA is modulated in irradiated mouse skin and that LEP itself is significantly modulated by irradiation in human epithelial cell lines and in breast cancer tissues from radiotherapy-treated patients. These results confirm and extend the previous evidence that LEP has a general and important role in the response of mammalian cells to irradiation.

  8. Alteration of proliferation and apoptotic markers in normal and premalignant tissue associated with prostate cancer

    International Nuclear Information System (INIS)

    Ananthanarayanan, Vijayalakshmi; Deaton, Ryan J; Yang, Ximing J; Pins, Michael R; Gann, Peter H

    2006-01-01

    Molecular markers identifying alterations in proliferation and apoptotic pathways could be particularly important in characterizing high-risk normal or pre-neoplastic tissue. We evaluated the following markers: Ki67, Minichromosome Maintenance Protein-2 (Mcm-2), activated caspase-3 (a-casp3) and Bcl-2 to determine if they showed differential expression across progressive degrees of intraepithelial neoplasia and cancer in the prostate. To identify field effects, we also evaluated whether high-risk expression patterns in normal tissue were more common in prostates containing cancer compared to those without cancer (supernormal), and in histologically normal glands adjacent to a cancer focus as opposed to equivalent glands that were more distant. The aforementioned markers were studied in 13 radical prostatectomy (RP) and 6 cystoprostatectomy (CP) specimens. Tissue compartments representing normal, low grade prostatic intraepithelial neoplasia (LGPIN), high grade prostatic intraepithelial neoplasia (HGPIN), as well as different grades of cancer were mapped on H&E slides and adjacent sections were analyzed using immunohistochemistry. Normal glands within 1 mm distance of a tumor focus and glands beyond 5 mm were considered 'near' and 'far', respectively. Randomly selected nuclei and 40 × fields were scored by a single observer; basal and luminal epithelial layers were scored separately. Both Ki-67 and Mcm-2 showed an upward trend from normal tissue through HGPIN and cancer with a shift in proliferation from basal to luminal compartment. Activated caspase-3 showed a significant decrease in HGPIN and cancer compartments. Supernormal glands had significantly lower proliferation indices and higher a-casp3 expression compared to normal glands. 'Near' normal glands had higher Mcm-2 indices compared to 'far' glands; however, they also had higher a-casp3 expression. Bcl-2, which varied minimally in normal tissue, did not show any trend

  9. In vitro radiation response studies on bone marrow fibroblasts (CFU-F) obtained from normal and chronically irradiated dogs

    International Nuclear Information System (INIS)

    Klein, A.K.; Stitzel, K.A.; Greenberg, B.; Woo, L.

    1984-01-01

    The radiation resistance of bone marrow fibroblasts as measured by their proliferative potential was evaluated in chronically irradiated dogs. Bone marrows were obtained from eight dogs that had been chronically irradiated beginning at 21 days of gestation or after birth and eight age-matched controls. Of these irradiated dogs, four were either preleukemic or exhibited frank acute nonlymphocytic leukemia. The other four were clinically normal but demonstrated abnormalities in their marrow that could be attributed to radiation effects and/or other pathologic changes. Fibroblasts from six of the irradiated dogs were significantly more radioresistant than those of their controls. Five of these six dogs subsequently succumbed to hematopathologic disease, while the two irradiated dogs with normal fibroblasts remained clinically normal, suggesting that this observed radioresistance may be linked to the disease process. (author)

  10. Radionuclide investigation of the blood flow in tumor and normal rat tissues in induced hyperglycemia

    International Nuclear Information System (INIS)

    Istomin, Yu.P.; Shitikov, B.D.; Markova, L.V.

    1991-01-01

    Radionuclide angiography was performed in rats with transplantable tumors. Induced hyperglycemia was shown to result in blood flow inhibition in tumor and normal tissues of tumor-bearing rats. Some differences were revealed in a degree of reversibility of blood flow disorders in tissues of the above strains. The results obtained confirmed the advisability of radiation therapy at the height of a decrease in tumor blood

  11. Responses of some normal tissues to low doses of γ-radiation

    International Nuclear Information System (INIS)

    Withers, H.R.

    1975-01-01

    The response of four normal tissues to low doses of γ-radiation was measured in mice using three indirect methods. The survival curves for cells of the tissues studied (colon, jejunum, testis and haemoleucopoietic system) may be exponential over an uncertain dose range (from zero to between 100 to 230 rad), the slope being about one third of that in the high-dose region. Some of the uncertainties in the data probably reflect variations in age-density distribution. (author)

  12. Trace elemental correlation study in malignant and normal breast tissue by PIXE technique

    International Nuclear Information System (INIS)

    Raju, G.J. Naga; Sarita, P.; Kumar, M. Ravi; Murty, G.A.V. Ramana; Reddy, B. Seetharami; Lakshminarayana, S.; Vijayan, V.; Lakshmi, P.V.B. Rama; Gavarasana, Satyanarayana; Reddy, S. Bhuloka

    2006-01-01

    Particle induced X-ray emission technique was used to study the variations in trace elemental concentrations between normal and malignant human breast tissue specimens and to understand the effects of altered homeostasis of these elements in the etiology of breast cancer. A 3 MeV proton beam was used to excite the biological samples of normal and malignant breast tissues. The elements Cl, K, Ca, Ti, Cr, Mn, Fe, Ni, Cu, Zn, As, Se, Br, Rb and Sr were identified and their relative concentrations were estimated. Almost all the elements were found to be elevated (p < 0.05, Wilcoxon signed-ranks test) in the cancerous tissues when compared with normal tissues. The excess levels of trace elements observed in the cancerous breast tissues could either be a cause or a consequence of breast cancer. Regarding their role in the initiation or promotion of breast cancer, one possible interpretation is that the elevated levels of Cu, Fe and Cr could have led to the formation of free radicals or other reactive oxygen species (ROS) that adversely affect DNA thereby causing breast cancer, which is mainly attributed to genetic abnormalities. Moreover, since Cu and Fe are required for angiogenesis, elevated concentrations of these elements are likely to promote breast cancer by increasing the blood supply for tumor growth. On the other hand elevated concentrations of elements in breast cancer tissues might also be a consequence of the cancer. This can be understood in terms of the biochemical and histological differences between normal and cancerous breast tissues. Tumors, characterized by unregulated multiplication of cells, need an ever-increasing supply of essential nutrients including trace elements. This probably results in an increased vascularity of malignant tissues, which in turn leads to enhancement of elemental concentrations in tumors

  13. Immunohistochemical analysis of oxidative stress and DNA repair proteins in normal mammary and breast cancer tissues

    International Nuclear Information System (INIS)

    Curtis, Carol D; Thorngren, Daniel L; Nardulli, Ann M

    2010-01-01

    During the course of normal cellular metabolism, oxygen is consumed and reactive oxygen species (ROS) are produced. If not effectively dissipated, ROS can accumulate and damage resident proteins, lipids, and DNA. Enzymes involved in redox regulation and DNA repair dissipate ROS and repair the resulting damage in order to preserve a functional cellular environment. Because increased ROS accumulation and/or unrepaired DNA damage can lead to initiation and progression of cancer and we had identified a number of oxidative stress and DNA repair proteins that influence estrogen responsiveness of MCF-7 breast cancer cells, it seemed possible that these proteins might be differentially expressed in normal mammary tissue, benign hyperplasia (BH), ductal carcinoma in situ (DCIS) and invasive breast cancer (IBC). Immunohistochemistry was used to examine the expression of a number of oxidative stress proteins, DNA repair proteins, and damage markers in 60 human mammary tissues which were classified as BH, DCIS or IBC. The relative mean intensity was determined for each tissue section and ANOVA was used to detect statistical differences in the relative expression of BH, DCIS and IBC compared to normal mammary tissue. We found that a number of these proteins were overexpressed and that the cellular localization was altered in human breast cancer tissue. Our studies suggest that oxidative stress and DNA repair proteins not only protect normal cells from the damaging effects of ROS, but may also promote survival of mammary tumor cells

  14. Adipose Tissues Characteristics of Normal, Obesity, and Type 2 Diabetes in Uygurs Population

    Directory of Open Access Journals (Sweden)

    Jun Zhang

    2015-01-01

    Full Text Available Our results showed that, at the same BMI level, Uygurs have greater WHR values, abdominal visceral fat content, and diabetes risks than Kazaks. In addition, values of HDL-C in Uygur subjects were lower than those in Kazak subjects, and values of creatinine, uric acid, diastolic blood pressure, blood glucose, and fructosamine in Uygur male subjects were lower than those in Kazak male subjects. In contrast, systolic blood pressure values in Uygur subjects were greater than those in Kazak subjects, and blood glucose values were greater in Uygur female subjects than in Kazak female subjects. Additionally, in Uygurs, visceral adipose tissue expression levels of TBX1 and TCF21 were greater in obesity group than in normal and T2DM groups and lower in T2DM group than in normal group (P<0.01. The visceral adipose tissue expression levels of APN in normal group was greater than those in obesity and T2DM groups, and visceral adipose tissue expression levels of TNF-α and MCP-1 in normal group were lower than those in obesity and T2DM groups (P<0.01. In conclusion, T2DM in Uygurs was mainly associated with not only distribution of adipose tissue in body, but also change in metabolic activity and adipocytokines secretion of adipose tissue.

  15. Modification of the biologic dose to normal tissue by daily fraction

    Energy Technology Data Exchange (ETDEWEB)

    Wollin, M; Kagan, A R [Southern California Permanente Medical Group, Los Angeles Calif. (USA). Dep. of Radiation Therapy

    1976-12-01

    A method to predict normal tissue injury is proposed that includes high daily doses and unusual times successfully by calculating a new value called BIR (Biologic Index of Reaction). BIR and NSD were calculated for various normal tissue reactions. With the aid of statistical correlation techniques it is found that the BIR model is better than the NSD model in predicting radiation myelopathy and vocal edema and as good as NSD IN PREDICTING RIB FRACTURE/ Neither model predicts pericardial effusion. In no case were the results of BIR inferior to those of NSD.

  16. The expression of Egfl7 in human normal tissues and epithelial tumors.

    Science.gov (United States)

    Fan, Chun; Yang, Lian-Yue; Wu, Fan; Tao, Yi-Ming; Liu, Lin-Sen; Zhang, Jin-Fan; He, Ya-Ning; Tang, Li-Li; Chen, Guo-Dong; Guo, Lei

    2013-04-23

    To investigate the expression of Egfl7 in normal adult human tissues and human epithelial tumors.
 RT-PCR and Western blot were employed to detect Egfl7 expression in normal adult human tissues and 10 human epithelial tumors including hepatocellular carcinoma (HCC), lung cancer, breast cancer, prostate cancer, colorectal cancer, gastric cancer, esophageal cancer, malignant glioma, ovarian cancer and renal cancer. Immunohistochemistry and cytoimmunofluorescence were subsequently used to determine the localization of Egfl7 in human epithelial tumor tissues and cell lines. ELISA was also carried out to examine the serum Egfl7 levels in cancer patients. In addition, correlations between Egfl7 expression and clinicopathological features as well as prognosis of HCC and breast cancer were also analyzed on the basis of immunohistochemistry results.
 Egfl7 was differentially expressed in 19 adult human normal tissues and was overexpressed in all 10 human epithelial tumor tissues. The serum Egfl7 level was also significantly elevated in cancer patients. The increased Egfl7 expression in HCC correlated with vein invasion, absence of capsule formation, multiple tumor nodes and poor prognosis. Similarly, upregulation of Egfl7 in breast cancer correlated strongly with TNM stage, lymphatic metastasis, estrogen receptor positivity, Her2 positivity and poor prognosis. 
 Egfl7 is significantly upregulated in human epithelial tumor tissues, suggesting Egfl7 to be a potential biomarker for human epithelial tumors, especially HCC and breast cancer.

  17. Modulatory Role of Aloe vera on Gamma Irradiation Induced Histological Changes in Different Tissues of Rats

    International Nuclear Information System (INIS)

    Rezk, R.G.

    2005-01-01

    Aloe Vera is known for its wide medicinal properties. This study was performed to evaluate the role of Aloe vera (Aloe barbadensis Miller) in the amelioration of the histological disorders that occurr in different tissues of albino rats exposed to 7 Gy whole body gamma irradiation, delivered as a single dose. Aloe vera (leaf juice filtrate) was supplemented daily to rats (0.25 ml/kg b wt/day) by gavage, 5 days before irradiation and 10 days after irradiation. Experimental investigations performed 7 and 10 days after exposure to radiation showed that Aloe vera treatment has significantly improved the radiation-induced inflammation, haemorrhage, widening and dilated blood vessela, necrosis, atrophy sloughing in liver, spleen and small intestine (jejenum) tissues of irradiated rats. It is concluded that the synergistic relationship between the elements found in the leaf of Aloe vera could be a useful adjunct for maintaining the integrity of histological architecture

  18. Immunological investigations of antigens released by normal and irradiated schistosomasa mansoni cercariae in vitro. Part of a coordinated programme on preparation of irradiated vaccines against some human diseases

    International Nuclear Information System (INIS)

    Catty, D.

    1982-07-01

    S.mansoni cercariae were γ-irradiated at 1-15 K rads, syringe transformed, and injected into groups of 20 mice (200 dose), with unirradiated controls. Aliquots of 1,500 cercariae irradiated at 1-40 K rads (plus unirradiated controls) were cultured in serum-free medium. It was found that irradiation does not inhibit release of a broad spectrum of antigens in culture over 6 hours until 20 K rads is delivered. Mice used as hosts for the graded cercarial irradiation vaccine were subdivided into groups of 10 and either left unchallenged or challenged at 6 weeks with a normal infection of 200 cercariae. Serum samples were taken from every mouse at regular intervals and antibodies titrated by solid phase radioimmunoassay. Injected parasites, whether irradiated or normal, always gave higher antibody titres to cercarial and egg antigens than the equivalent dose of normal (challenge) parasites infecting by the natural route. Challenge infection depressed anti-cercarial responses in mice exposed to irradiated larvae but boosted the response to normal injected parasites. Antibodies to SEA were in lower titre in all groups but rose from week 7 (1 week post-challenge) in the groups injected with normal and 1 K rad-treated parasites, where adults were previously established in the hosts. At 12 weeks all mice were sacrificed and perfused for adults. Egg yields in liver and intestine were determined. There was no evidence of protective immunity to challenge infection induced by injected unirradiated or 1 K rad-irradiated, transformed, cercariae, even though both sources of parasite gave rise to egg-laying adults. By contrast, the 5, 10 and 15 K rad vaccines gave protection of 36-49%, even though they gave rise to no persistent adults or any deposited eggs. The protective (immunising) properties of irradiation-attenuated vaccines of S.mansoni cercariae can thus be clearly correlated with their capacity to release antigens in the immediate post irradiation period

  19. Correlation study of trace metals in malignant and normal breast tissues by AAS technique

    International Nuclear Information System (INIS)

    Rahman, S.

    2012-01-01

    The study reports the application of atomic absorption spectrophotometry (AAS) for quantification of Fe, Cu and Zn in forty one formalin-fixed biopsy breast carcinoma tissue and adjoining fifteen normal tissue samples. These tissues samples were of category two breast carcinoma patients and of normal subjects. The qualitative comparison between the elements levels measured in the two types of specimens suggests significant elevation of these metals in the histopathological samples of carcinoma tissue. The samples were collected from women aged 19-51 years. Most of the patients belong to urban areas of Pakistan and middle to high socioeconomic status with the exception of few. Findings of study depicts that these elements have an important role in the initiation and development of carcinoma as consistent pattern of elevation for Fe, Cu and Zn was observed. The results showed the excessive accumulation of Fe (166.9 mg/L) in tissue samples of breast carcinoma patients (p < 0.01) than that in normal tissues samples (23.5 mg/L). In order to validate our method of analysis certified reference material Muscle Tissue Lyophilised (IAEA) MA-M-2/TM was analyzed for Fe, Cu and Zn. Determined concentrations were in good agreement with certified levels. The concentration distribution of trace elements Cu, Zn and Fe measured in the malignant tissues were found to be higher when compared to benign tissues, indicating the involvement of these metals in the breast malignancy. Results also indicate that excess iron may play a role in breast carcinogenesis. (Orig./A.B.)

  20. Effect of taurine on the insuline secretion isolated by the pancreatic tissue of intact and irradiated rats

    International Nuclear Information System (INIS)

    Dokshina, G.A.; Silaeva, T.Yu.

    1976-01-01

    The whole-body irradiation of rats (700 rads) inhibits the secretory activity of insular pancreatic tissue. Administration of taurine (200 mg/kg), on the fifth day after irradiation, five times every second day normalizes the secretory function of pancreatic islands. In the experiments in vitro, taurine (1.5 and 3.0 mg/ml) stimulated hormone secretion. The stimulating action of the amino acid manifests itself when β-receptors are blocked by obsidane (0.5 μg/ml). It is suggested that insuline secretion by β-cells of pancreas is restored and enhanced by taurine not merely through the adenylatecyclase system; other ways are also possible

  1. Effect of taurine on the insuline secretion isolated by the pancreatic tissue of intact and irradiated rats

    Energy Technology Data Exchange (ETDEWEB)

    Dokshina, G A; Silaeva, T Yu [Tomskij Gosudarstvennyj Univ. (USSR). Nauchno-Issledovatel' skij Inst. Biologii i Biofiziki

    1976-05-01

    The whole-body irradiation of rats (700 rads) inhibits the secretory activity of insular pancreatic tissue. Administration of taurine (200 mg/kg), on the fifth day after irradiation, five times every second day normalizes the secretory function of pancreatic islands. In the experiments in vitro, taurine (1.5 and 3.0 mg/ml) stimulated hormone secretion. The stimulating action of the amino acid manifests itself when ..beta..-receptors are blocked by obsidane (0.5 ..mu..g/ml). It is suggested that insuline secretion by ..beta..-cells of pancreas is restored and enhanced by taurine not merely through the adenylatecyclase system; other ways are also possible.

  2. Reconstruction with vascularized composite tissue in patients with excessive injury following surgery and irradiation

    International Nuclear Information System (INIS)

    Serafin, D.; DeLand, M.; Lesesne, C.B.; Smith, P.J.; Noell, K.T.; Georgiade, N.

    1982-01-01

    The biological effects of a single high dose of radiation are examined. Both cellular injury and repair are reviewed during early, intermediate, and late phases. Anticipated composite tissue morbidity is detailed for therapeutic radiation doses administered to the head and neck, breast and thorax, and perineum. Patients who demonstrated excessive time-dose fractionation values were irradiated with lower x-ray energies. Those in whom there was an overlap of treatment fields presented a serious challenge to the reconstructive surgeon. Judicious selection of well-vascularized composite tissue outside the portals of irradiation, preferably with a long vascular pedicle, facilitated reconstruction. When possible, both donor and recipient vasculature should be outside the irradiated area to ensure uninterrupted blood flow to the transferred or transplanted tissue

  3. Optical redox imaging indices discriminate human breast cancer from normal tissues

    Science.gov (United States)

    Xu, He N.; Tchou, Julia; Feng, Min; Zhao, Huaqing; Li, Lin Z.

    2016-01-01

    Abstract. Our long-term goal was to investigate the potential of incorporating redox imaging technique as a breast cancer (BC) diagnosis component to increase the positive predictive value of suspicious imaging finding and to reduce unnecessary biopsies and overdiagnosis. We previously found that precancer and cancer tissues in animal models displayed abnormal mitochondrial redox state. We also revealed abnormal mitochondrial redox state in cancerous specimens from three BC patients. Here, we extend our study to include biopsies of 16 patients. Tissue aliquots were collected from both apparently normal and cancerous tissues from the affected cancer-bearing breasts shortly after surgical resection. All specimens were snap-frozen and scanned with the Chance redox scanner, i.e., the three-dimensional cryogenic NADH/Fp (reduced nicotinamide adenine dinucleotide/oxidized flavoproteins) fluorescence imager. We found both Fp and NADH in the cancerous tissues roughly tripled that in the normal tissues (predox ratio Fp/(NADH + Fp) was ∼27% higher in the cancerous tissues (predox ratio alone could predict cancer with reasonable sensitivity and specificity. Our findings suggest that the optical redox imaging technique can provide parameters independent of clinical factors for discriminating cancer from noncancer breast tissues in human patients. PMID:27896360

  4. Extracranial soft-tissue swelling: a normal postmortem radiographic finding or a sign of trauma?

    International Nuclear Information System (INIS)

    Strouse, P.J.; Caplan, M.; Owings, C.L.

    1998-01-01

    Objective. To determine if extracranial soft-tissue swelling is an expected postmortem finding or a sign of trauma. Materials and methods. Extracranial soft-tissue thickness was measured at 5 standardized locations on postmortem skull films obtained of 18 infants with no evidence of trauma on autopsy. The same measurements were performed on the skull films of 100 living children, all less than 3 years old and without clinical history of trauma. Results. Extracranial soft tissues measured only slightly greater in the postmortem group than on films of living children; however, the difference did achieve statistical significance. Conclusion. Minimal extracranial soft-tissue swelling is a normal finding on a postmortem skeletal survey. The presence of substantial or asymmetric extracranial soft-tissue swelling should be viewed with suspicion for trauma. (orig.)

  5. Extracranial soft-tissue swelling: a normal postmortem radiographic finding or a sign of trauma?

    Energy Technology Data Exchange (ETDEWEB)

    Strouse, P.J. [Section of Pediatric Radiology, University of Michigan Medical Center, Ann Arbor (United States); Caplan, M. [Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan (United States); Owings, C.L. [Department of Pediatrics and Communicable Diseases, C. S. Mott Children`s Hospital, Ann Arbor, Michigan (United States)

    1998-08-01

    Objective. To determine if extracranial soft-tissue swelling is an expected postmortem finding or a sign of trauma. Materials and methods. Extracranial soft-tissue thickness was measured at 5 standardized locations on postmortem skull films obtained of 18 infants with no evidence of trauma on autopsy. The same measurements were performed on the skull films of 100 living children, all less than 3 years old and without clinical history of trauma. Results. Extracranial soft tissues measured only slightly greater in the postmortem group than on films of living children; however, the difference did achieve statistical significance. Conclusion. Minimal extracranial soft-tissue swelling is a normal finding on a postmortem skeletal survey. The presence of substantial or asymmetric extracranial soft-tissue swelling should be viewed with suspicion for trauma. (orig.) With 2 tabs., 5 refs.

  6. A Cancer-Indicative microRNA Pattern in Normal Prostate Tissue

    Directory of Open Access Journals (Sweden)

    Thorsten Schlomm

    2013-03-01

    Full Text Available We analyzed the levels of selected micro-RNAs in normal prostate tissue to assess their potential to indicate tumor foci elsewhere in the prostate. Histologically normal prostate tissue samples from 31 prostate cancer patients and two cancer negative control groups with either unsuspicious or elevated prostate specific antigen (PSA levels (14 and 17 individuals, respectively were analyzed. Based on the expression analysis of 157 microRNAs in a pool of prostate tissue samples and information from data bases/literature, we selected eight microRNAs for quantification by real-time polymerase chain reactions (RT-PCRs. Selected miRNAs were analyzed in histologically tumor-free biopsy samples from patients and healthy controls. We identified seven microRNAs (miR-124a, miR-146a & b, miR-185, miR-16 and let-7a & b, which displayed significant differential expression in normal prostate tissue from men with prostate cancer compared to both cancer negative control groups. Four microRNAs (miR-185, miR-16 and let-7a and let-7b remained to significantly discriminate normal tissues from prostate cancer patients from those of the cancer negative control group with elevated PSA levels. The transcript levels of these microRNAs were highly indicative for the presence of cancer in the prostates, independently of the PSA level. Our results suggest a microRNA-pattern in histologically normal prostate tissue, indicating prostate cancer elsewhere in the organ.

  7. Blue light irradiation-induced oxidative stress in vivo via ROS generation in rat gingival tissue.

    Science.gov (United States)

    Yoshida, Ayaka; Shiotsu-Ogura, Yukako; Wada-Takahashi, Satoko; Takahashi, Shun-suke; Toyama, Toshizo; Yoshino, Fumihiko

    2015-10-01

    It has been reported that oxidative stress with reactive oxygen species (ROS) generation is induced by blue light irradiation to a living body. Only limited research has been reported in dental field on the dangers of blue light, mostly focusing on cytotoxicity associated with heat injury of dental pulp. We thus performed an in vivo study on oral tissue exposed to blue light. ROS generated upon blue light irradiation of flavin adenine dinucleotide were measured by electron spin resonance spectroscopy. After blue light irradiation, the palatal gingiva of Wistar rats were isolated. Collected samples were subjected to biochemical analysis of lipid peroxidation and glutathione. Singlet oxygen was generated by blue light irradiation, but was significantly quenched in an N-acetyl-L-cysteine (NAC) concentration-dependent manner. Blue light significantly accelerated oxidative stress and increased the oxidized glutathione levels in gingival tissue. These effects were also inhibited by NAC pre-administration. The results suggest that blue light irradiation at clinical levels of tooth bleaching treatment may enhance lipid peroxidation by the induction of oxidative stress and the consumption of a significant amount of intracellular glutathione. In addition, NAC might be an effective supplement for the protection of oral tissues against blue light irradiation-induced oxidative damage. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. Modification of PLGA Nanofibrous Mats by Electron Beam Irradiation for Soft Tissue Regeneration

    Directory of Open Access Journals (Sweden)

    Jae Baek Lee

    2015-01-01

    Full Text Available Biodegradable poly(lactide-co-glycolide (PLGA has found widespread use in modern medical practice. However, the degradation rate of PLGA should be adjusted for specific biomedical applications such as tissue engineering, drug delivery, and surgical implantation. This study focused on the effect of electron beam radiation on nanofibrous PLGA mats in terms of physical properties and degradation behavior with cell proliferation. PLGA nanofiber mats were prepared by electrospinning, and electron beam was irradiated at doses of 50, 100, 150, 200, 250, and 300 kGy. PLGA mats showed dimensional integrity after electron beam irradiation without change of fiber diameter. The degradation behavior of a control PLGA nanofiber (0 kGy and electron beam-irradiated PLGA nanofibers was analyzed by measuring the molecular weight, weight loss, change of chemical structure, and fibrous morphology. The molecular weight of the PLGA nanofibers decreased with increasing electron beam radiation dose. The mechanical properties of the PLGA nanofibrous mats were decreased with increasing electron beam irradiation dose. Cell proliferation behavior on all electron beam irradiated PLGA mats was similar to the control PLGA mats. Electron beam irradiation of PLGA nanofibrous mats is a potentially useful approach for modulating the biodegradation rate of tissue-specific nonwoven nanofibrous scaffolds, specifically for soft tissue engineering applications.

  9. Pelvic Normal Tissue Contouring Guidelines for Radiation Therapy: A Radiation Therapy Oncology Group Consensus Panel Atlas

    Energy Technology Data Exchange (ETDEWEB)

    Gay, Hiram A., E-mail: hgay@radonc.wustl.edu [Washington University School of Medicine, St Louis, MO (United States); Barthold, H. Joseph [Commonwealth Hematology and Oncology, Weymouth, MA (United States); Beth Israel Deaconess Medical Center, Boston, MA (Israel); O' Meara, Elizabeth [Radiation Therapy Oncology Group, Philadelphia, PA (United States); Bosch, Walter R. [Washington University School of Medicine, St Louis, MO (United States); El Naqa, Issam [Department of Radiation Oncology, McGill University Health Center, Montreal, Quebec (Canada); Al-Lozi, Rawan [Washington University School of Medicine, St Louis, MO (United States); Rosenthal, Seth A. [Radiation Oncology Centers, Radiological Associates of Sacramento, Sacramento, CA (United States); Lawton, Colleen [Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, WI (United States); Lee, W. Robert [Department of Radiation Oncology, Duke University Medical Center, Durham, NC (United States); Sandler, Howard [Cedars-Sinai Medical Center, Los Angeles, CA (United States); Zietman, Anthony [Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA (United States); Myerson, Robert [Washington University School of Medicine, St Louis, MO (United States); Dawson, Laura A. [Department of Radiation Oncology, Princess Margaret Hospital, University of Toronto, Toronto, Ontario (Canada); Willett, Christopher [Department of Radiation Oncology, Duke University Medical Center, Durham, NC (United States); Kachnic, Lisa A. [Department of Radiation Oncology, Boston Medical Center, Boston University School of Medicine, Boston, MA (United States); Jhingran, Anuja [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX (United States); Portelance, Lorraine [University of Miami, Miami, FL (United States); Ryu, Janice [Radiation Oncology Centers, Radiological Associates of Sacramento, Sacramento, CA (United States); and others

    2012-07-01

    Purpose: To define a male and female pelvic normal tissue contouring atlas for Radiation Therapy Oncology Group (RTOG) trials. Methods and Materials: One male pelvis computed tomography (CT) data set and one female pelvis CT data set were shared via the Image-Guided Therapy QA Center. A total of 16 radiation oncologists participated. The following organs at risk were contoured in both CT sets: anus, anorectum, rectum (gastrointestinal and genitourinary definitions), bowel NOS (not otherwise specified), small bowel, large bowel, and proximal femurs. The following were contoured in the male set only: bladder, prostate, seminal vesicles, and penile bulb. The following were contoured in the female set only: uterus, cervix, and ovaries. A computer program used the binomial distribution to generate 95% group consensus contours. These contours and definitions were then reviewed by the group and modified. Results: The panel achieved consensus definitions for pelvic normal tissue contouring in RTOG trials with these standardized names: Rectum, AnoRectum, SmallBowel, Colon, BowelBag, Bladder, UteroCervix, Adnexa{sub R}, Adnexa{sub L}, Prostate, SeminalVesc, PenileBulb, Femur{sub R}, and Femur{sub L}. Two additional normal structures whose purpose is to serve as targets in anal and rectal cancer were defined: AnoRectumSig and Mesorectum. Detailed target volume contouring guidelines and images are discussed. Conclusions: Consensus guidelines for pelvic normal tissue contouring were reached and are available as a CT image atlas on the RTOG Web site. This will allow uniformity in defining normal tissues for clinical trials delivering pelvic radiation and will facilitate future normal tissue complication research.

  10. Differential Expression of Cytochrome P450 Enzymes in Normal and Tumor Tissues from Childhood Rhabdomyosarcoma

    Science.gov (United States)

    Molina-Ortiz, Dora; Camacho-Carranza, Rafael; González-Zamora, José Francisco; Shalkow-Kalincovstein, Jaime; Cárdenas-Cardós, Rocío; Ností-Palacios, Rosario; Vences-Mejía, Araceli

    2014-01-01

    Intratumoral expression of genes encoding Cytochrome P450 enzymes (CYP) might play a critical role not only in cancer development but also in the metabolism of anticancer drugs. The purpose of this study was to compare the mRNA expression patterns of seven representative CYPs in paired tumor and normal tissue of child patients with rabdomyosarcoma (RMS). Using real time quantitative RT-PCR, the gene expression pattern of CYP1A1, CYP1A2, CYP1B1, CYP2E1, CYP2W1, CYP3A4, and CYP3A5 were analyzed in tumor and adjacent non-tumor tissues from 13 child RMS patients. Protein concentration of CYPs was determined using Western blot. The expression levels were tested for correlation with the clinical and pathological data of the patients. Our data showed that the expression levels of CYP1A1 and CYP1A2 were negligible. Elevated expression of CYP1B1 mRNA and protein was detected in most RMS tumors and adjacent normal tissues. Most cancerous samples exhibit higher levels of both CYP3A4 and CYP3A5 compared with normal tissue samples. Expression of CYP2E1 mRNA was found to be significantly higher in tumor tissue, however no relation was found with protein levels. CYP2W1 mRNA and/or protein are mainly expressed in tumors. In conclusion, we defined the CYP gene expression profile in tumor and paired normal tissue of child patients with RMS. The overexpression of CYP2W1, CYP3A4 and CYP3A5 in tumor tissues suggests that they may be involved in RMS chemoresistance; furthermore, they may be exploited for the localized activation of anticancer prodrugs. PMID:24699256

  11. The Influence of Tissue Lyophilization and Gamma Irradiation on the Solubility of Proteins

    International Nuclear Information System (INIS)

    Komender, J.; Jendyk, J.; Leibschang, J.

    1967-01-01

    Most recent methods of tissue preservation are based on lyophilization and sterilization with gamma rays. Unfortunately the tissues preserved by this method lose their viability, this being connected with protein denaturation. The denaturing influence either of lyophilization or sterilization with gamma rays on different materials has been described. However, no observations on denaturation of proteins in prepared grafts are known. The work aimed at establishing the influence of individual stages of the procedure used in a tissue bank on the solubility of proteins. An experiment was performed using rat liver as a model tissue. Solubility of protein was determined in five groups of material, as follows: (1) fresh tissue, used as a control, (2) frozen tissue, (3) frozen and lyophilized tissue, (4) frozen, lyophilized and irradiated tissue, and (5) fresh irradiated tissue. Folin's method was used for determination of protein in water extracts of tissues. It was found that: (1) the whole procedure considerably diminished the protein solubility, (2) freezing diminishes the protein solubility by 35% on average, (3) lyophilization causes no further protein denaturation, (4) protein solubility is reduced most (by about 65%) by sterilization with gamma rays. (author)

  12. Effects of x-ray irradiation on mast cells and mastocalcergy in the connective tissue

    Energy Technology Data Exchange (ETDEWEB)

    Song, H. Y.; Rhee, S. J.; Son, M. H.; Choi, K. C. [Chonbuk National University College of Medicine, Jeonju (Korea, Republic of)

    1982-09-15

    Experiments were performed to observe the influence of x-ray irradiation on mast cells and mastocalcergy in rats. Animals were irradiated single dose of x-ray. X-ray irradiation was applied to the whole body in doses either 100 rads or 150 rads (Cobalt-60 Teletherapy Unit). One day after irradiation the rats were injected lead acetate intravenously, followed by injection of compound 48/80 in the back subcutaneously. Animals were killed by decapitation at intervals, 1 hour, 5 hours, 1 day and 6 day after subcutaneous injection. Specimens of the abdominal and back skin were fixed in alcohol formol solution and stained with the following methods; H-E for observation of pathological changes of tissues, toluidine blue for demonstration of mast cells, von Kossa-azure A for demonstration of carbonate and phosphate, and chloranilic acid for demonstration of calcium. The following conclusions were obtained. Calciphylatic wheals are large size in the control group, medium size in 100 rads irradiation group and small size in 150 rads irradiation group. In x-ray irradiation groups the number of mast cells decreases more in the 150 rads than in the 100 rads irradiation. In the 100 rads x-ray irradiation group, histochemical study of the injection sites showed that calcium impregnated to mast cell granules and connective tissue fibers in 1 days after subcutaneous injection. The morphogenesis of this calcinosis was the same in the rat of 5 hour after subcutaneous injection of the control group. Whereas, 1 day after subcutaneous injection in 150 rads x-ray irradiation group calcium deposited more slightly than other groups.

  13. Analysis of DNA vulnerability to damage, repair and degradation in tissues of irradiated animals

    International Nuclear Information System (INIS)

    Ryabchenko, N.I.; Ivannik, B.P.

    1982-01-01

    Single-strand and paired ruptures of DNA were found to result in appearance of locally denaturated areas in its secondary structure and to disordered protein-DNA interaction. It was shown with the use of the viscosimeter method of measuring the molecular mass of single stranded high-polymeric DNA that cells of various tissues by the intensity of DNA repair can be divided into two groups, rapid- and slow-repair ones. Tissue specificity of enzyme function of the repair systems and systems responsible for post-irradiation DNA degradation depends on the activity of endonucleases synthesized by the cells both in health and in their irradiation-induced synthesis

  14. In vivo evidence for an endothelium-dependent mechanism in radiation-induced normal tissue injury

    Science.gov (United States)

    Rannou, Emilie; François, Agnès; Toullec, Aurore; Guipaud, Olivier; Buard, Valérie; Tarlet, Georges; Mintet, Elodie; Jaillet, Cyprien; Iruela-Arispe, Maria Luisa; Benderitter, Marc; Sabourin, Jean-Christophe; Milliat, Fabien

    2015-01-01

    The pathophysiological mechanism involved in side effects of radiation therapy, and especially the role of the endothelium remains unclear. Previous results showed that plasminogen activator inhibitor-type 1 (PAI-1) contributes to radiation-induced intestinal injury and suggested that this role could be driven by an endothelium-dependent mechanism. We investigated whether endothelial-specific PAI-1 deletion could affect radiation-induced intestinal injury. We created a mouse model with a specific deletion of PAI-1 in the endothelium (PAI-1KOendo) by a Cre-LoxP system. In a model of radiation enteropathy, survival and intestinal radiation injury were followed as well as intestinal gene transcriptional profile and inflammatory cells intestinal infiltration. Irradiated PAI-1KOendo mice exhibited increased survival, reduced acute enteritis severity and attenuated late fibrosis compared with irradiated PAI-1flx/flx mice. Double E-cadherin/TUNEL labeling confirmed a reduced epithelial cell apoptosis in irradiated PAI-1KOendo. High-throughput gene expression combined with bioinformatic analyses revealed a putative involvement of macrophages. We observed a decrease in CD68+cells in irradiated intestinal tissues from PAI-1KOendo mice as well as modifications associated with M1/M2 polarization. This work shows that PAI-1 plays a role in radiation-induced intestinal injury by an endothelium-dependent mechanism and demonstrates in vivo that the endothelium is directly involved in the progression of radiation-induced enteritis. PMID:26510580

  15. Stem Cell Therapy to Reduce Radiation-Induced Normal Tissue Damage

    NARCIS (Netherlands)

    Coppes, Rob P.; van der Goot, Annemieke; Lombaert, Isabelle M. A.

    Normal tissue damage after radiotherapy is still a major problem in cancer treatment. Stem cell therapy may provide a means to reduce radiation-induced side effects and improve the quality of life of patients. This review discusses the current status in stem cell research with respect to their

  16. Tumor control and normal tissue toxicity: The two faces of radiotherapy

    NARCIS (Netherlands)

    van Oorschot, B.

    2016-01-01

    This thesis discusses the two contrasting sides of radiotherapy: tumor control and normal tissue toxicity. On one hand, radiation treatment aims to target the tumor with the highest possible radiation dose, inducing as much lethal DNA damage as possible. On the other hand however, escalation of the

  17. Effect-independent measures of tissue responses to fractionated irradiation

    International Nuclear Information System (INIS)

    Thames, H.D. Jr.

    1984-01-01

    Tissue repair factors measure the sparing that can be achieved from dose fractionation in the absence of proliferation. Four repair factors are analysed in these terms: Fsub(R),Fsub(rec), the ratio of linear-quadratic survival model parameters β/α and the half-time Tsub(1/2) for intracellular repair processes. Theoretically, Fsub(R) and Fsub(rec) are increasing functions of D 1 , and thus depend on level of effect. This is confirmed by analysis of skin reactions after multifractionated radiation. By contrast, β/α is effect-independent as a measure of repair capacity in skin, gut, and bone marrow, tissues for which it is reasonable to assume that survival of identifiable target cells is the primary determinant of the endpoint. For a functional endpoint not clearly connected with the depletion of a specific target-cell population (late fibrotic reactions in the kidney), there was an increase in β/α with increased levels of injury, but this was statistically insignificant. Tsub(1/2) is independent of fraction size in skin, gut, and spinal cord, and is longer (1.5 hours) in the late-reacting tissues (lung and spinal cord) than in those that react acutely (Tsub(1/2) less than 1 hour), with skin as the exception (Tsub(1/2) approx. 1.3 hours). (author)

  18. Increasing the temporal resolution of direct normal solar irradiance forecasted series

    Science.gov (United States)

    Fernández-Peruchena, Carlos M.; Gastón, Martin; Schroedter-Homscheidt, Marion; Marco, Isabel Martínez; Casado-Rubio, José L.; García-Moya, José Antonio

    2017-06-01

    A detailed knowledge of the solar resource is a critical point in the design and control of Concentrating Solar Power (CSP) plants. In particular, accurate forecasting of solar irradiance is essential for the efficient operation of solar thermal power plants, the management of energy markets, and the widespread implementation of this technology. Numerical weather prediction (NWP) models are commonly used for solar radiation forecasting. In the ECMWF deterministic forecasting system, all forecast parameters are commercially available worldwide at 3-hourly intervals. Unfortunately, as Direct Normal solar Irradiance (DNI) exhibits a great variability due to the dynamic effects of passing clouds, 3-h time resolution is insufficient for accurate simulations of CSP plants due to their nonlinear response to DNI, governed by various thermal inertias due to their complex response characteristics. DNI series of hourly or sub-hourly frequency resolution are normally used for an accurate modeling and analysis of transient processes in CSP technologies. In this context, the objective of this study is to propose a methodology for generating synthetic DNI time series at 1-h (or higher) temporal resolution from 3-h DNI series. The methodology is based upon patterns as being defined with help of the clear-sky envelope approach together with a forecast of maximum DNI value, and it has been validated with high quality measured DNI data.

  19. Tumor and normal tissue responses to fractioned non-uniform dose delivery

    Energy Technology Data Exchange (ETDEWEB)

    Kaellman, P; Aegren, A; Brahme, A [Karolinska Inst., Stockholm (Sweden). Dept. of Radiation Physics

    1996-08-01

    The volume dependence of the radiation response of a tumor is straight forward to quantify because it depends primarily on the eradication of all its clonogenic cells. A tumor therefore has a parallel organization as any surviving clonogen in principle can repopulate the tumor. The difficulty with the response of the tumor is instead to know the density and sensitivity distribution of the most resistant clonogenic cells. The increase in the 50% tumor control dose and the decrease in the maximum normalized slope of the dose response relation, {gamma}, in presence of small compartments of resistant tumor cells have therefore been quantified to describe their influence on the dose response relation. Injury to normal tissue is a much more complex and gradual process. It depends on earlier effects induced long before depletion of the differentiated and clonogenic cells that in addition may have a complex structural and functional organization. The volume dependence of the dose response relation of normal tissues is therefore described here by the relative seriality, s, of the infrastructure of the organ. The model can also be generalized to describe the response of heterogeneous tissues to non uniform dose distributions. The new model is compared with clinical and experimental data on normal tissue response, and shows good agreement both with regard to the shape of dose response relation and the volume dependence of the isoeffect dose. The response of tumors and normal tissues are quantified for arbitrary dose fractionations using the linear quadratic cell survival parameters {alpha} and {beta}. The parameters of the dose response relation are derived both for a constant dose per fraction and a constant number of dose fractions, thus in the latter case accounting also for non uniform dose delivery. (author). 26 refs, 4 figs.

  20. Improvement of potato tolerance to salinity using tissue culture techniques and irradiation with in vitro selection

    International Nuclear Information System (INIS)

    Al-Safadi, B.; Arabi, M. I. E.

    2005-06-01

    A mutation breeding program was conducted to improve potato (Solanum tuberosum) tolerance to salinity. In vitro cultured explants from potato cvs. Draga, Diamant, Spunta were irradiated with gamma doses 25, 30, and 35 Gy.Growing shoots were cut and re-cultured every 2 weeks until the 4th generation (MV 4 ) to make sure no chimeral tissues still existed in the mutant material. Plantlets were subsequently propagated to obtain enough explants for in vitro selection pressure. Around 3000 plantlets from the three cultivars were subjected to selection pressure. MV 4 explants were cultured on MS medium supplemented with the NaCl in varying concentrations ranging between 50 to 200 mM. Surviving plantlets were propagated and re-cultured on a similar medium to insure their tolerance to salinity. Tolerant plantlets were acclimatized and transferred to pots and grown under glasshouse conditions. Plants were later subjected to another selection pressure, by irrigating them using water containing NaCl in concentrations ranging between 50-250 mM in addition to controls irrigated with normal water. Cultivar Spunta produced the highest number of tolerant plants. Four plants of Spunta appeared to be tolerant to salinity whereas only one plant from Diamant and was tolerant and no plants from cultivar Draga were tolerant. Mutant plants varied in number of produced minitubers from 8 - 14. Also, weight of these minitubers varied from less than 1 to 31 grams. (author)

  1. LYCOPENE EFFICIENCY IN THE MODULATION OF OXIDATIVE DAMAGE IN DIFFERENT TISSUES OF GAMMA IRRADIATED RATS

    International Nuclear Information System (INIS)

    EL-TAHAWY, N.A.; NADA, A.S.; REZK, R.G.

    2008-01-01

    Exposure to ionizing radiation induces oxidative stress that has been recognized as an important etiological factor in the causation of several chronic diseases. Lycopene, a carotenoid almost exclusively present in tomatoes and tomatoes products, is a lipid soluble antioxidant claimed to possess cardio protective and anticancer properties. The present study was designed to determine the possible modulator effects of lycopene on radiation-induced oxidative damage to liver, spleen and lung tissues. Animals were supplemented with lycopene (5 mg/kg body weight/ day) by gavages for two weeks before whole body exposure to gamma rays and within the period of irradiation (3 successive doses, each of 3 Gy at 72 hours intervals). Animals were sacrificed on the 3 r d day post the last irradiation session.The results obtained in the present study showed that whole body gamma irradiation produced oxidative stress manifested by significant elevation in lipid peroxides levels measured as thiobarbituric acid reactive substances (TBARS) associated with significant decrease of nitric oxide (NO) content. Non-significant change in total cupper (Cu) in the three tissues was recorded while significant increase of total iron (Fe) was observed in liver and spleen tissues only. Liver tissue of irradiated rats showed significant decrease in the activities of the antioxidant enzymes as superoxide dismutase (SOD) and catalase (CAT). In spleen tissues, there was a significant increase of SOD and significant decrease of CAT activities while in lung tissues, both SOD and CAT activities showed significant increase.Histological observations of photomicrograph of liver sections showed that radiation-induced sever damage obvious by dilated portal vein, ruptured hepatocytes, necrotic, pyknotic, karyolitic nuclei and vacuolated cytoplasm. In spleen tissue, radiation was induced degeneration of lymphatic nodules, dilation follicular artery and marked hemorrhage. In lung tissue, radiation- induces ill

  2. The Edinburgh experience of treating sarcomas of soft tissues and bone with neutron irradiation

    International Nuclear Information System (INIS)

    Duncan, W.; Arnott, S.J.; Jack, W.J.L.

    1986-01-01

    The experience of treating 30 patients with sarcomas of soft tissue and bone with d(15)+Be neutron irradiation is reported. The local control of measurable soft-tissue sarcomas was 38.5% (minimum follow-up 2 years), which is similar to that expected after photon therapy. The radiation morbidity was unacceptably high (50%). Bone tumours did not respond well; in only one out of nine was lasting local tumour control achieved. (author)

  3. Damaging and protective bystander cross-talk between human lung cancer and normal cells after proton microbeam irradiation

    International Nuclear Information System (INIS)

    Desai, Sejal; Kobayashi, Alisa; Konishi, Teruaki; Oikawa, Masakazu; Pandey, Badri N.

    2014-01-01

    Graphical abstract: - Highlights: • Proton-microbeam irradiated A549 cells send damaging signals to bystander A549 cells. • Irradiated A549–A549 bystander response is through gap junctional communication. • Bystander WI38 cells exert protective signalling in irradiated A549 cells. • Rescue of irradiated A549 cells by WI38 cells is independent of gap junctions. - Abstract: Most of the studies of radiation-induced bystander effects (RIBE) have been focused on understanding the radiobiological changes observed in bystander cells in response to the signals from irradiated cells in a normal cell population with implications to radiation risk assessment. However, reports on RIBE with relevance to cancer radiotherapy especially investigating the bidirectional and criss-cross bystander communications between cancer and normal cells are limited. Hence, in present study employing co-culture approach, we have investigated the bystander cross-talk between lung cancer (A549) and normal (WI38) cells after proton-microbeam irradiation using γ-H2AX foci fluorescence as a measure of DNA double-strand breaks (DSBs). We observed that in A549–A549 co-cultures, irradiated A549 cells exert damaging effects in bystander A549 cells, which were found to be mediated through gap junctional intercellular communication (GJIC). However, in A549–WI38 co-cultures, irradiated A549 did not affect bystander WI38 cells. Rather, bystander WI38 cells induced inverse protective signalling (rescue effect) in irradiated A549 cells, which was independent of GJIC. On the other hand, in response to irradiated WI38 cells neither of the bystander cells (A549 or WI38) showed significant increase in γ-H2AX foci. The observed bystander signalling between tumour and normal cells may have potential implications in therapeutic outcome of cancer radiotherapy

  4. Damaging and protective bystander cross-talk between human lung cancer and normal cells after proton microbeam irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Desai, Sejal [Radiation Signalling and Cancer Biology Section, Radiation Biology and Health Sciences Division, Bhabha Atomic Research Centre, Mumbai 400 085 (India); Kobayashi, Alisa; Konishi, Teruaki; Oikawa, Masakazu [Radiation System and Engineering Section, Department of Technical Support and Development, Research, Development and Support Center, National Institute of Radiological Sciences, Chiba 263-8555 (Japan); Pandey, Badri N., E-mail: badrinarain@yahoo.co.in [Radiation Signalling and Cancer Biology Section, Radiation Biology and Health Sciences Division, Bhabha Atomic Research Centre, Mumbai 400 085 (India)

    2014-05-15

    Graphical abstract: - Highlights: • Proton-microbeam irradiated A549 cells send damaging signals to bystander A549 cells. • Irradiated A549–A549 bystander response is through gap junctional communication. • Bystander WI38 cells exert protective signalling in irradiated A549 cells. • Rescue of irradiated A549 cells by WI38 cells is independent of gap junctions. - Abstract: Most of the studies of radiation-induced bystander effects (RIBE) have been focused on understanding the radiobiological changes observed in bystander cells in response to the signals from irradiated cells in a normal cell population with implications to radiation risk assessment. However, reports on RIBE with relevance to cancer radiotherapy especially investigating the bidirectional and criss-cross bystander communications between cancer and normal cells are limited. Hence, in present study employing co-culture approach, we have investigated the bystander cross-talk between lung cancer (A549) and normal (WI38) cells after proton-microbeam irradiation using γ-H2AX foci fluorescence as a measure of DNA double-strand breaks (DSBs). We observed that in A549–A549 co-cultures, irradiated A549 cells exert damaging effects in bystander A549 cells, which were found to be mediated through gap junctional intercellular communication (GJIC). However, in A549–WI38 co-cultures, irradiated A549 did not affect bystander WI38 cells. Rather, bystander WI38 cells induced inverse protective signalling (rescue effect) in irradiated A549 cells, which was independent of GJIC. On the other hand, in response to irradiated WI38 cells neither of the bystander cells (A549 or WI38) showed significant increase in γ-H2AX foci. The observed bystander signalling between tumour and normal cells may have potential implications in therapeutic outcome of cancer radiotherapy.

  5. Radiobiological influence of megavoltage electron pulses of ultra-high pulse dose rate on normal tissue cells.

    Science.gov (United States)

    Laschinsky, Lydia; Karsch, Leonhard; Leßmann, Elisabeth; Oppelt, Melanie; Pawelke, Jörg; Richter, Christian; Schürer, Michael; Beyreuther, Elke

    2016-08-01

    Regarding the long-term goal to develop and establish laser-based particle accelerators for a future radiotherapeutic treatment of cancer, the radiobiological consequences of the characteristic short intense particle pulses with ultra-high peak dose rate, but low repetition rate of laser-driven beams have to be investigated. This work presents in vitro experiments performed at the radiation source ELBE (Electron Linac for beams with high Brilliance and low Emittance). This accelerator delivered 20-MeV electron pulses with ultra-high pulse dose rate of 10(10) Gy/min either at the low pulse frequency analogue to previous cell experiments with laser-driven electrons or at high frequency for minimizing the prolonged dose delivery and to perform comparison irradiation with a quasi-continuous electron beam analogue to a clinically used linear accelerator. The influence of the different electron beam pulse structures on the radiobiological response of the normal tissue cell line 184A1 and two primary fibroblasts was investigated regarding clonogenic survival and the number of DNA double-strand breaks that remain 24 h after irradiation. Thereby, no considerable differences in radiation response were revealed both for biological endpoints and for all probed cell cultures. These results provide evidence that the radiobiological effectiveness of the pulsed electron beams is not affected by the ultra-high pulse dose rates alone.

  6. Radiobiological influence of megavoltage electron pulses of ultra-high pulse dose rate on normal tissue cells

    International Nuclear Information System (INIS)

    Laschinsky, Lydia; Karsch, Leonhard; Schuerer, Michael; Lessmann, Elisabeth; Beyreuther, Elke; Oppelt, Melanie; Pawelke, Joerg; Richter, Christian

    2016-01-01

    Regarding the long-term goal to develop and establish laser-based particle accelerators for a future radiotherapeutic treatment of cancer, the radiobiological consequences of the characteristic short intense particle pulses with ultra-high peak dose rate, but low repetition rate of laser-driven beams have to be investigated. This work presents in vitro experiments performed at the radiation source ELBE (Electron Linac for beams with high Brilliance and low Emittance). This accelerator delivered 20-MeV electron pulses with ultra-high pulse dose rate of 10"1"0 Gy/min either at the low pulse frequency analogue to previous cell experiments with laser-driven electrons or at high frequency for minimizing the prolonged dose delivery and to perform comparison irradiation with a quasi-continuous electron beam analogue to a clinically used linear accelerator. The influence of the different electron beam pulse structures on the radiobiological response of the normal tissue cell line 184A1 and two primary fibroblasts was investigated regarding clonogenic survival and the number of DNA double-strand breaks that remain 24 h after irradiation. Thereby, no considerable differences in radiation response were revealed both for biological endpoints and for all probed cell cultures. These results provide evidence that the radiobiological effectiveness of the pulsed electron beams is not affected by the ultra-high pulse dose rates alone. (orig.)

  7. Comparison of SUVs normalized by lean body mass determined by CT with those normalized by lean body mass estimated by predictive equations in normal tissues

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Woo Hyoung; Kim, Chang Guhn; Kim, Dae Weung [Wonkwang Univ. School of Medicine, Iksan (Korea, Republic of)

    2012-09-15

    Standardized uptake values (SUVs)normalized by lean body mass (LBM)determined by CT were compared with those normalized by LBM estimated using predictive equations (PEs)in normal liver, spleen, and aorta using {sup 18}F FDG PET/CT. Fluorine 18 fluorodeoxyglucose (F FDG)positron emission tomography/computed tomography (PET/CT)was conducted on 453 patients. LBM determined by CT was defined in 3 ways (LBM{sup CT1}-3). Five PEs were used for comparison (LBM{sup PE1}-5). Tissue SUV normalized by LBM (SUL) was calculated using LBM from each method (SUL{sup CT1}-3, SUL{sup PE1}-5). Agreement between methods was assessed by Bland Altman analysis. Percentage difference and percentage error were also calculated. For all liver SUL{sup CTS} vs. liver SUL{sup PES} except liver SUL{sup PE3}, the range of biases, SDs of percentage difference and percentage errors were -0.17-0.24 SUL, 6.15-10.17%, and 25.07-38.91%, respectively. For liver SUL{sup CTs} vs. liver SUL{sup PE3}, the corresponding figures were 0.47-0.69 SUL, 10.90-11.25%, and 50.85-51.55%, respectively, showing the largest percentage errors and positive biases. Irrespective of magnitudes of the biases, large percentage errors of 25.07-51.55% were observed between liver SUL{sup CT1}-3 and liver SUL{sup PE1}-5. The results of spleen and aorta SUL{sup CTs} and SUL{sup PEs} comparison were almost identical to those for liver. The present study demonstrated substantial errors in individual SUL{sup PEs} compared with SUL{sup CTs} as a reference value. Normalization of SUV by LBM determined by CT rather than PEs may be a useful approach to reduce errors in individual SUL{sup PEs}.

  8. Comparison of SUVs normalized by lean body mass determined by CT with those normalized by lean body mass estimated by predictive equations in normal tissues

    International Nuclear Information System (INIS)

    Kim, Woo Hyoung; Kim, Chang Guhn; Kim, Dae Weung

    2012-01-01

    Standardized uptake values (SUVs)normalized by lean body mass (LBM)determined by CT were compared with those normalized by LBM estimated using predictive equations (PEs)in normal liver, spleen, and aorta using 18 F FDG PET/CT. Fluorine 18 fluorodeoxyglucose (F FDG)positron emission tomography/computed tomography (PET/CT)was conducted on 453 patients. LBM determined by CT was defined in 3 ways (LBM CT1 -3). Five PEs were used for comparison (LBM PE1 -5). Tissue SUV normalized by LBM (SUL) was calculated using LBM from each method (SUL CT1 -3, SUL PE1 -5). Agreement between methods was assessed by Bland Altman analysis. Percentage difference and percentage error were also calculated. For all liver SUL CTS vs. liver SUL PES except liver SUL PE3 , the range of biases, SDs of percentage difference and percentage errors were -0.17-0.24 SUL, 6.15-10.17%, and 25.07-38.91%, respectively. For liver SUL CTs vs. liver SUL PE3 , the corresponding figures were 0.47-0.69 SUL, 10.90-11.25%, and 50.85-51.55%, respectively, showing the largest percentage errors and positive biases. Irrespective of magnitudes of the biases, large percentage errors of 25.07-51.55% were observed between liver SUL CT1 -3 and liver SUL PE1 -5. The results of spleen and aorta SUL CTs and SUL PEs comparison were almost identical to those for liver. The present study demonstrated substantial errors in individual SUL PEs compared with SUL CTs as a reference value. Normalization of SUV by LBM determined by CT rather than PEs may be a useful approach to reduce errors in individual SUL PEs

  9. Elemental concentration analysis in PCa, BPH and normal prostate tissues using SR-TXRF

    International Nuclear Information System (INIS)

    Leitao, Roberta G.; Anjos, Marcelino J.; Canellas, Catarine G.L.; Lopes, Ricardo T.

    2009-01-01

    Prostate cancer (PCa) is one of the main causes of illness and death all over the world. In Brazil, prostate cancer currently represents the second most prevalent malignant neoplasia in men, representing 21% of all cancer cases. Benign Prostate Hyperplasia (BPH) is an illness prevailing in men above the age of 50, close to 90% after the age of 80. The prostate presents a high zinc concentration, about 10-fold higher than any other body tissue. In this work, samples of human prostate tissues with cancer (PCa), BPH and normal tissue were analyzed utilizing the total reflection X-ray fluorescence spectroscopy using synchrotron radiation technique (SRTXRF) to investigate the differences in the elemental concentrations in these tissues. SR-TXRF analyses were performed at the X-Ray fluorescence beamline at Brazilian National Synchrotron Light Laboratory (LNLS), in Campinas, Sao Paulo. It was possible to determine the concentrations of the following elements: P, S, K, Ca, Fe, Cu, Zn, Br and Rb. By using Mann-Whitney U test it was observed that almost all elements presented concentrations with significant differences α = 0.05) between the groups studied. The elements and groups were: S, K, Ca, Fe, Zn, Br and Rb (PCa X Normal); S, Fe, Zn and Br (PCa X BPH); K, Ca, Fe, Zn, Br and Rb (BPH X Normal). (author)

  10. Human Colors-The Rainbow Garden of Pathology: What Gives Normal and Pathologic Tissues Their Color?

    Science.gov (United States)

    Piña-Oviedo, Sergio; Ortiz-Hidalgo, Carlos; Ayala, Alberto G

    2017-03-01

    - Colors are important to all living organisms because they are crucial for camouflage and protection, metabolism, sexual behavior, and communication. Human organs obviously have color, but the underlying biologic processes that dictate the specific colors of organs and tissues are not completely understood. A literature search on the determinants of color in human organs yielded scant information. - To address 2 specific questions: (1) why do human organs have color, and (2) what gives normal and pathologic tissues their distinctive colors? - Endogenous colors are the result of complex biochemical reactions that produce biologic pigments: red-brown cytochromes and porphyrins (blood, liver, spleen, kidneys, striated muscle), brown-black melanins (skin, appendages, brain nuclei), dark-brown lipochromes (aging organs), and colors that result from tissue structure (tendons, aponeurosis, muscles). Yellow-orange carotenes that deposit in lipid-rich tissues are only produced by plants and are acquired from the diet. However, there is lack of information about the cause of color in other organs, such as the gray and white matter, neuroendocrine organs, and white tissues (epithelia, soft tissues). Neoplastic tissues usually retain the color of their nonneoplastic counterpart. - Most available information on the function of pigments comes from studies in plants, microorganisms, cephalopods, and vertebrates, not humans. Biologic pigments have antioxidant and cytoprotective properties and should be considered as potential future therapies for disease and cancer. We discuss the bioproducts that may be responsible for organ coloration and invite pathologists and pathology residents to look at a "routine grossing day" with a different perspective.

  11. Association between Single Nucleotide Polymorphisms in XRCC3 and Radiation-Induced Adverse Effects on Normal Tissue: A Meta-Analysis.

    Directory of Open Access Journals (Sweden)

    Yu-Zhe Song

    Full Text Available The X-ray repair cross-complementing group 3 (XRCC3 protein plays an important role in the repair of DNA double-strand breaks. The relationship between XRCC3 polymorphisms and the risk of radiation-induced adverse effects on normal tissue remains inconclusive. Thus, we performed a meta-analysis to elucidate the association between XRCC3 polymorphisms and radiation-induced adverse effects on normal tissue. All eligible studies up to December 2014 were identified through a search of the PubMed, Embase and Web of Science databases. Seventeen studies involving 656 cases and 2193 controls were ultimately included in this meta-analysis. The pooled odds ratios (ORs with corresponding 95% confidence intervals (CIs were calculated to evaluate the association between XRCC3 polymorphisms and the risk of radiation-induced normal tissue adverse effects. We found that the XRCC3 p.Thr241Met (rs861539 polymorphism was significantly associated with early adverse effects induced by radiotherapy (OR = 1.99, 95%CI: 1.31-3.01, P = 0.001. A positive association lacking statistical significance with late adverse effects was also identified (OR = 1.28, 95%CI: 0.97-1.68, P = 0.08. In addition, the rs861539 polymorphism was significantly correlated with a higher risk of adverse effects induced by head and neck area irradiation (OR = 2.41, 95%CI: 1.49-3.89, p = 0.0003 and breast irradiation (OR = 1.41, 95%CI: 1.02-1.95, p = 0.04, whereas the correlation was not significant for lung irradiation or pelvic irradiation. Furthermore, XRCC3 rs1799794 polymorphism may have a protective effect against late adverse effects induced by radiotherapy (OR = 0.47, 95%CI: 0.26-0.86, P = 0.01. Well-designed large-scale clinical studies are required to further validate our results.

  12. Fusarium growth on culture media made of tissue juice from irradiated and unirradiated potato tubers

    International Nuclear Information System (INIS)

    Taczanowski, M.

    1994-01-01

    Fusarium Sulphureum Schlecht is one of the tuber pathogens causing potato storage disease knowing as dry rot. Because irradiation can disturb the tissue defence mechanism against the pathogen, it was decided to carry out experiments on influence of the treatment on subsequent tuber tissue reaction to a maceration process. The maceration as a physical stress was a substitute for the pathogen activity. Tubers of two potato varieties were tested: Mila -a resistant variety to Fusarium and Atol - susceptible one. Tubers of both varieties were irradiated with a dose of 105 kGy. Unirradiated tubers were taken as a control. A day after irradiation the cortex tissue was macerated using an ordinary rasper and the resulted tissue pulp was strained through medical gauze to obtain crude juice. The juice was clarified by centrifugation and then added to dissolved PDA. The volume ratio of juice to PDA was 1:1. The prepared media were dispensed into Petri dishes. Small pieces of the Fusarium culture were put on the surface of the medium at the centre of each Petri dish. Subsequent growth of the fungus was assessed by measurement of culture diameters every 24 hours. Linear functions of the Fusarium growth were obtained for Mila control and Atol control. In the case of Mila, the Fusarium found more favourable conditions for its growth in the presence of juice from irradiated tubers than from the control ones. Making the same comparison for Atol, no difference was detected. (author)

  13. Whole-body γ-irradiation effects on catecholamine concentration in animal tissues

    International Nuclear Information System (INIS)

    Makashev, Zh.K.; Uteshev, T.A.; Abylaev, Zh. A.; Zhurnist, A.G.

    2003-01-01

    On the whole-body gamma-radiation activity in the exchanges of catecholamines (adrenalin and non-adrenalin) and their predecessors (dopamine and DOPA) in the rats tissue organism, indicate the infringement of irradiated animals in different links of biological synthesis the bio-gen amines in different phases of the radiation: DOPA→dopamine, dopamine→adrenalin, adrenalin→non-adrenalin. (author)

  14. Lewis x is highly expressed in normal tissues: a comparative immunohistochemical study and literature revision.

    Science.gov (United States)

    Croce, María V; Isla-Larrain, Marina; Rabassa, Martín E; Demichelis, Sandra; Colussi, Andrea G; Crespo, Marina; Lacunza, Ezequiel; Segal-Eiras, Amada

    2007-01-01

    An immunohistochemical analysis was employed to determine the expression of carbohydrate antigens associated to mucins in normal epithelia. Tissue samples were obtained as biopsies from normal breast (18), colon (35) and oral cavity mucosa (8). The following carbohydrate epitopes were studied: sialyl-Lewis x, Lewis x, Lewis y, Tn hapten, sialyl-Tn and Thomsen-Friedenreich antigen. Mucins were also studied employing antibodies against MUC1, MUC2, MUC4, MUC5AC, MUC6 and also normal colonic glycolipid. Statistical analysis was performed and Kendall correlations were obtained. Lewis x showed an apical pattern mainly at plasma membrane, although cytoplasmic staining was also found in most samples. TF, Tn and sTn haptens were detected in few specimens, while sLewis x was found in oral mucosa and breast tissue. Also, normal breast expressed MUC1 at a high percentage, whereas MUC4 was observed in a small number of samples. Colon specimens mainly expressed MUC2 and MUC1, while most oral mucosa samples expressed MUC4 and MUC1. A positive correlation between MUC1VNTR and TF epitope (r=0.396) was found in breast samples, while in colon specimens MUC2 and colonic glycolipid versus Lewis x were statistically significantly correlated (r=0.28 and r=0.29, respectively). As a conclusion, a defined carbohydrate epitope expression is not exclusive of normal tissue or a determined localization, and it is possible to assume that different glycoproteins and glycolipids may be carriers of carbohydrate antigens depending on the tissue localization considered.

  15. Hematopoietic tissue repair under chronic low daily dose irradiation

    International Nuclear Information System (INIS)

    Seed, T.M.

    1994-01-01

    The capacity of the hematopoietic system to repair constantly accruing cellular damage under chronic, low daily dose gamma irradiation is essential for the maintenance of a functional hematopoietic system, and, in turn, long term survival. In certain individuals, however, such continuous cycles of damage and repair provide an essential inductive environment for selected types of hematopathologies, e.g., myeloid leukemia (ML). We have been studying temporal and causal relationships between hematopoietic capacity, associated repair functions, and propensities for hematologic disease in canines under variable levels of chronic radiation stress (0.3-26.3 cGy d -1 ). Results indicate that the maximum exposure rate tolerated by the hematopoietic system is highly individual-specific and is based largely on the degree to which repair capacity, and, in turn, hematopoietic restoration, is augmented under chronic exposure. In low-tolerance individuals (prone to aplastic anemia, subgroup (1), the failure to augment basic m-pair functions seemingly results in a progressive accumulation of genetic and cellular damage within vital progenitorial marrow compartments particularly marked within erythroid compartments. that results in loss of reproductive capacity and ultimately in collapse of the hematopoietic system. The high-tolerance individuals (radioaccomodated and either prone- or not prone to ML, subgroup 2 ampersand 3 appear to minimize the accumulating damage effect of daily exposures by extending repair functions, which preserves reproductive integrity and fosters regenerative hematopoietic responses. As the strength of the regenerative response manifests the extent of repair augmentation, the relatively strong response of high- tolerance individuals progressing to patent ML suggests an insufficiency of repair quality rather than repair quantity

  16. 2-deoxyglucose tissue levels and insulin levels following tolazamide dosing in normal and obese mice

    International Nuclear Information System (INIS)

    Skillman, C.A.; Fletcher, H.P.

    1986-01-01

    The effect of tolazamide (TZ), a sulfonylurea, on 14 C-2-deoxyglucose ( 14 C-2DG) tissue distribution and insulin levels of normal and obese mice was investigated using an in vivo physiological method. Acute doses of TZ (50 mg/kg ip) increased 14 C-2DG levels in gastrocnemius muscle and retroperitoneal fat and produced a transient elevation of insulin which most likely accounts for the increased 14 C-2DG levels in muscle and fat. The results demonstrate that the in vivo 14 C-2DG method produced results consistent with known actions of sulfonylureas on in vitro hexose assimilation in muscle and fat. Subchronic treatment (7 days) with TZ 50 mg/kg ip twice daily did not result in increased insulin-stimulated 14 C-2DG tissue levels in normal mice when compared to saline treated controls. However, insulin levels were lower in mice treated subchronically with TZ compared to saline controls suggesting an enhancement of insulin action. Viable yellow obese mice represent a model of maturity onset obesity presenting with insulin resistance. The insulin resistance of this obese strain appears to reside in the fat tissue as assessed by comparing 14 C-2DG tissue levels of obese mice with lean littermate controls. Subchronic TZ treatment had no effect on 14 C-2DG uptake in fat or muscle tissue of viable yellow obese mice and did not alter their plasma insulin levels. It appears that genetically obese viable mice may be resistant to subchronic treatment with TZ. (author)

  17. Distribution of the anticancer drugs doxorubicin, mitoxantrone and topotecan in tumors and normal tissues.

    Science.gov (United States)

    Patel, Krupa J; Trédan, Olivier; Tannock, Ian F

    2013-07-01

    Pharmacokinetic analyses estimate the mean concentration of drug within a given tissue as a function of time, but do not give information about the spatial distribution of drugs within that tissue. Here, we compare the time-dependent spatial distribution of three anticancer drugs within tumors, heart, kidney, liver and brain. Mice bearing various xenografts were treated with doxorubicin, mitoxantrone or topotecan. At various times after injection, tumors and samples of heart, kidney, liver and brain were excised. Within solid tumors, the distribution of doxorubicin, mitoxantrone and topotecan was limited to perivascular regions at 10 min after administration and the distance from blood vessels at which drug intensity fell to half was ~25-75 μm. Although drug distribution improved after 3 and 24 h, there remained a significant decrease in drug fluorescence with increasing distance from tumor blood vessels. Drug distribution was relatively uniform in the heart, kidney and liver with substantially greater perivascular drug uptake than in tumors. There was significantly higher total drug fluorescence in the liver than in tumors after 10 min, 3 and 24 h. Little to no drug fluorescence was observed in the brain. There are marked differences in the spatial distributions of three anticancer drugs within tumor tissue and normal tissues over time, with greater exposure to most normal tissues and limited drug distribution to many cells in tumors. Studies of the spatial distribution of drugs are required to complement pharmacokinetic data in order to better understand and predict drug effects and toxicities.

  18. Kinetics of [14C-5] 8-methoxypsoralen uptake by UVA irradiated and non-irradiated rabbit eye tissues

    International Nuclear Information System (INIS)

    Malinin, G.I.; Glew, W.B.; Roberts, W.P.; Nigra, T.P.

    1981-01-01

    Total 8-methoxypsoralen (8-MOP) in intact and UVA irradiated rabbit eye tissues and its unaltered fraction in aqueous and eye lenses were determined over the 24 hours after i.v. injection of [ 14 C-5] and carrier 8-MOP at the concentration of 50 microCi and 5 mg/kg. No 8-MOP was detected at the end of 24 hours in intact and irradiated aqueous, vitreous and retina in contrast to one hour when the respective levels were congruent to 220, greater than 0 and congruent to 160 ng/g. Eye-plasma drug concentration ratios were less than 0.5 initially, but increased thereafter. While the average lens 8-MOP levels of congruent to 140 ng/g remained unchanged for 24 hours, no unaltered drug was detected beyond eight hours. Measurable amounts of label at the end of 24 hours also persisted in the cornea, iris, sclera and conjunctiva

  19. The effect of setup uncertainty on normal tissue sparing with IMRT for head-and-neck cancer

    International Nuclear Information System (INIS)

    Manning, Matthew A.; Wu Quiwen; Cardinale, Robert M.; Mohan, Radhe; Lauve, Andrew D.; Kavanagh, Brian D.; Morris, Monica M.; Schmidt-Ullrich, Rupert K.

    2001-01-01

    coverage of the nodal region adjacent to the parotid gland. As expected, when the plans were shifted, the greatest increase in contralateral parotid irradiation was noted with shifts toward the contralateral parotid gland. With these shifts, the average volume of contralateral parotid receiving greater than 30 Gy was reduced from 22% to 4% when a PRV was used. This correlated with a reduction in the average normal-tissue complication probability (NTCP) from 22% to 7%. Conclusions: The use of PRV may limit the volume of normal tissue structures, such as the parotid gland, exceeding tolerance dose as a result of setup errors. Consequently, it will be important to incorporate the nomenclature of ICRU-62 into the design of future IMRT studies, if the clinical gains of increased normal-tissue sparing are to be realized

  20. Dose rate effect of 125I irradiation on normal rabbit eyes and experimental choroidal melanoma

    International Nuclear Information System (INIS)

    Yang, C.M.; Olsen, K.R.; Schwade, J.G.; Houdek, P.V.; Markoe, A.M.; Pisciotta, V.; Xiaodong Wu

    1993-01-01

    The dose rate effect of radiation by 125 I plaque on choroidal melanoma and normal intraocular tissue was studied. In the first part of the experiment, high activity plaques (HAP) and low activity plagues (LAP) were implanted on rabbit eyes with experimental Greene choroidal melanoma to deliver a total dose of 10 000 cGy to the tumor apex. The mean dose rate calculated at 0.5 mm from the inner sclera in eight eyes with high activity plaques was 3341.5 cGy hr -1 while that in ten eyes with low activity plaques was 239.9 cGy hr -1 . For tumors less than 1.0 mm in height, both groups showed complete tumor regression at the tumor implantation site after plaque treatment. For tumours more than 1.0 mm in height, two out of two eyes in the low activity plaque group and one of four eyes in the high activity plaque group failed to show complete tumor regression. In the second part of the experiment, 125 I plaques were implanted on the sclera of 12 normal rabbits' eyes. Six received high dose rate plaque treatment, while the other six received low dose rate plaque treatment. Clinical and histologic examinations demonstrated more damaging effects to the normal chorioretinal tissues at the plaque implantation site in the high dose rate plaque group. These results suggest that high dose rate plaques are more effective than low dose rate plaques when tumor height is statistically controlled. (Author)

  1. Effects of warm ischemic time on gene expression profiling in colorectal cancer tissues and normal mucosa.

    Directory of Open Access Journals (Sweden)

    Valeria Musella

    Full Text Available BACKGROUND: Genome-wide gene expression analyses of tumors are a powerful tool to identify gene signatures associated with biologically and clinically relevant characteristics and for several tumor types are under clinical validation by prospective trials. However, handling and processing of clinical specimens may significantly affect the molecular data obtained from their analysis. We studied the effects of tissue handling time on gene expression in human normal and tumor colon tissues undergoing routine surgical procedures. METHODS: RNA extracted from specimens of 15 patients at four time points (for a total of 180 samples after surgery was analyzed for gene expression on high-density oligonucleotide microarrays. A mixed-effects model was used to identify probes with different expression means across the four different time points. The p-values of the model were adjusted with the Bonferroni method. RESULTS: Thirty-two probe sets associated with tissue handling time in the tumor specimens, and thirty-one in the normal tissues, were identified. Most genes exhibited moderate changes in expression over the time points analyzed; however four of them were oncogenes, and two confirmed the effect of tissue handling by independent validation. CONCLUSIONS: Our results suggest that a critical time point for tissue handling in colon seems to be 60 minutes at room temperature. Although the number of time-dependent genes we identified was low, the three genes that already showed changes at this time point in tumor samples were all oncogenes, hence recommending standardization of tissue-handling protocols and effort to reduce the time from specimen removal to snap freezing accounting for warm ischemia in this tumor type.

  2. Models for radiation-induced tissue degeneration and conceptualization of rehabilitation of irradiated tissue by cell therapy

    International Nuclear Information System (INIS)

    Phulpin, Berengere

    2011-01-01

    Radiation therapy induced acute and late sequelae within healthy tissue included in the irradiated area. In general, lesions are characterized by ischemia, cell apoptosis and fibrosis. In this context, cell therapy using bone marrow mesenchymal stem cells (BMSC) might represent an attractive new therapeutic approach, based partly on their angiogenic ability and their involvement in the natural processes of tissue repair. The first part of this work consisted in the development of experimental mouse model of radio-induced tissue degeneration similar to that occurring after radiotherapy. The aim was to better understand the physiopathological mechanisms of radiation-induced tissue damage and to determine the best treatment strategy. The second part of this work investigated the feasibility of autologous BMSC therapy on the murine model of radiation previously established with emphasis on two pre-requisites: the retention of the injected cells within the target tissue and the evaluation of the graft on bone metabolism. This preclinical investigation in a mouse model constitutes an essential step allowing an evaluation of the benefit of cell therapy for the treatment of radiation-induced tissue injury. Data from these studies could allow the proposal of clinical studies [fr

  3. Study of temperature increase and optic depth penetration in photo irradiated human tissues

    International Nuclear Information System (INIS)

    Stolik, Suren; Delgado, Jose A.; Perez, Arllene M.; Anasagasti, Lorenzo

    2009-01-01

    Optical radiation is widely applied in the treatment and diagnosis of different pathologies. If the power density of the incident light is sufficiently high to induce a significant temperature rise in the irradiated tissue, then it is also needed the knowledge of the thermal properties of the tissue for a complete understanding of the therapeutic effects. The thermal penetration depth of several human tissues has been measured applying the diffusion approximation of the radiative transfer equation for the distribution of optical radiation. The method, the experimental setup and the results are presented and discussed. (Author)

  4. A hybrid electron and photon IMRT planning technique that lowers normal tissue integral patient dose using standard hardware.

    Science.gov (United States)

    Rosca, Florin

    2012-06-01

    technique (E+IMRT) can decrease the normal tissue integral dose compared to a photon-only IMRT plan. Different planning approaches can be enabled by the use of an electron beam directed toward organs at risk distal to the target, which are still spared due the rapid dose fall-off of the electron beam. Examples of such cases are the lateral electron beams in the thoracic region that do not irradiate the heart and contralateral lung, electron beams pointed toward kidneys in the abdominal region, or beams treating brain lesions pointed toward the brainstem or optical apparatus. For brain, electron vertex beams can also be used without irradiating the whole body. Since radiation retreatments become more and more common, minimizing the normal tissue integral dose and the dose delivered to tissues surrounding the target, as enabled by E+IMRT type techniques, should receive more attention. © 2012 American Association of Physicists in Medicine.

  5. Effect of heat and ionizing radiation on normal and neoplastic tissue of the C3H mouse

    International Nuclear Information System (INIS)

    Thrall, D.E.; Gillette, E.L.; Dewey, W.C.

    1975-01-01

    The radiation response of the skin of the C3H mouse was evaluated in terms of the dose of radiation required to produce moist desquamation completely surrounding the lower aspect of the hind leg by 21 days following irradiation (DD50-21). Irradiation of the leg under various conditions of local tissue oxygenation indicated that when the animals were breathing air (ambient conditions), the cells in the skin were not fully oxygenated. Heat was administered by immersing the leg for 15 min in 44.5 0 C water either immediately prior to or immediately following irradiation under various conditions of local tissue oxygenation. Heat administered following irradiation reduced the DD50-21 values by 724 rad for hyperbaric O 2 , 1210 rad for ambient, and 1656 rad for hypoxic conditions. Approximately these same rad equivalents were observed when heat was administered prior to irradiation, under hyperbaric O 2 and hypoxic conditions. However, administration of heat prior to irradiation under ambient conditions sensitized the cells to the effects of ionizing radiation. This sensitization was assumed to result from heat causing an increase in local tissue oxygenation prior to and at the time of irradiation. The effect of the heat dose administered under acute hypoxic conditions immediately prior to acute hypoxic irradiation was not significantly different from the protocol where heat was administered under ambient conditions immediately prior to acute hypoxic irradiation. This indicates an independence of the magnitude of the heat effect on the tissue oxygenation status at the time of heating. The response of the C3H mouse mammary adenocarcinoma to combined wet heat (Δ) and x radiation (X) administered under either hypoxic, ambient, or hyperbaric O 2 conditions of local tissue oxygenation was studied. (U.S.)

  6. Quantitative radiation dose-response relationships for normal tissues in man - I. Gustatory tissues response during photon and neutron radiotherapy

    International Nuclear Information System (INIS)

    Mossman, K.L.

    1982-01-01

    Quantitative radiation dose-response curves for normal gustatory tissue in man were studied. Taste function, expressed as taste loss, was evaluated in 84 patients who were given either photon or neutron radiotherapy for tumors in the head and neck region. Patients were treated to average tumor doses of 6600 cGy (photon) or 2200 cGy intervals for photon patients and 320-cGy intervals for neutron patients during radiotherapy. The dose-response curves for photons and neutrons were analyzed by fitting a four-parameter logistic equation to the data. Photon and neutron curves differed principally in their relative position along the dose axis. Comparison of the dose-response curves were made by determination of RBE. At 320 cGy, the lowest neutron dose at which taste measurements were made, RBE = 5.7. If this RBE is correct, then the therapeutic gain factor may be equal to or less than 1, indicating no biological advantage in using neutrons over photons for this normal tissue. These studies suggest measurements of taste function and evaluation of dose-response relationships may also be useful in quantitatively evaluating the efficacy of chemical modifiers of radiation response such as hypoxic cell radiosensitizers and radioprotectors

  7. Results of total lung irradiation and chemotherapy in comparison with partial lung irradiation in metastatic undifferentiated soft tissue sarcomas

    Energy Technology Data Exchange (ETDEWEB)

    Zamboglou, N.; Fuerst, G.; Pape, H.; Bannach, B.; Schmitt, G.; Molls, M.

    1988-07-01

    The poor prognosis of patients with unresectable pulmonary metastases of soft tissue sarcoma is well known. In order to evaluate the beneficial effect of radiotherapy, we have treated 44 patients with pulmonary metastases of grade 3 soft tissue sarcoma from 1980 to 1986. In 36 patients the treatment volume was restricted to the single metastases up to a dose of 50 to 60 (9 to 10 Gy/week). The survival rate at one year was 18% and at two years 6%. Eight patients were treated with a combined regimen, consisting of cisplatin and ifosfamide with simultaneous whole lung irradiation. Irradiation was performed with 8 or 16 MV photons at a hyperfractionation of 2x0,8 Gy/day (8 Gy/week). After a dose of 12 Gy, the single metastases were boosted up to 50 to 60 Gy, with a second course of chemotherapy. In six of eight patients complete remissions were achieved, one patient showed a partial remission. The survival rate at 27 months was 50%. The patients with partial remission died from pulmonary progression at 23 months. One patient died after twelve months from a loco-regional recurrence in the tonsillar fossa without evidence of pulmonary disease. Side effects included alopecia and moderate bone marrow suppression approximately twelve days after each chemotherapy cycle. Pulmonary fibrosis was observed only at the high dose volume without impairment of respiratory function. From these observations the conclusion is drawn that whole lung irradiation simultaneously with cisplatin and ifosfamide chemotherapy provides good palliative results without relevant morbidity in patients with high grade unresectable pulmonary metastases of soft tissue sarcomas.

  8. Chemical modification of conventional cancer radiotherapy. Tumor sensitization combined with normal tissue protection

    International Nuclear Information System (INIS)

    Kagiya, Tsutomu

    2006-01-01

    Nitrotriazole radiosensitizer, Sanazole (AK-2123, N-(2'-methoxyethyl)-2-(3''-nitro-1''-triazolyl) acetamide) developed by Kyoto University group was studied by 18 groups of 7 countries on fundamental aspects and clinical studies by 30 groups of 12 countries, and reported its effects on tumor sensitization of conventional cancer radiotherapy. On the other hand, the glucosides of vitamin C (Ascorbic acid glucoside, (AsAG) and water soluble derivative of vitamin-E (α-tocopherol glucoside, TMG) developed by Kyoto University group were studied fundamentally by 4 groups of 4 countries and clinically by 2 groups of 2 countries, and reported their effects on normal tissue protection in cancer treatments. These two studies of tumor sensitization and normal tissue protection were proposed as an advanced strategy of conventional cancer radiotherapy. (author)

  9. Improving normal tissue complication probability models: the need to adopt a "data-pooling" culture.

    Science.gov (United States)

    Deasy, Joseph O; Bentzen, Søren M; Jackson, Andrew; Ten Haken, Randall K; Yorke, Ellen D; Constine, Louis S; Sharma, Ashish; Marks, Lawrence B

    2010-03-01

    Clinical studies of the dependence of normal tissue response on dose-volume factors are often confusingly inconsistent, as the QUANTEC reviews demonstrate. A key opportunity to accelerate progress is to begin storing high-quality datasets in repositories. Using available technology, multiple repositories could be conveniently queried, without divulging protected health information, to identify relevant sources of data for further analysis. After obtaining institutional approvals, data could then be pooled, greatly enhancing the capability to construct predictive models that are more widely applicable and better powered to accurately identify key predictive factors (whether dosimetric, image-based, clinical, socioeconomic, or biological). Data pooling has already been carried out effectively in a few normal tissue complication probability studies and should become a common strategy. Copyright 2010 Elsevier Inc. All rights reserved.

  10. Thermal damage produced by high-irradiance continuous wave CO2 laser cutting of tissue.

    Science.gov (United States)

    Schomacker, K T; Walsh, J T; Flotte, T J; Deutsch, T F

    1990-01-01

    Thermal damage produced by continuous wave (cw) CO2 laser ablation of tissue in vitro was measured for irradiances ranging from 360 W/cm2 to 740 kW/cm2 in order to investigate the extent to which ablative cooling can limit tissue damage. Damage zones thinner than 100 microns were readily produced using single pulses to cut guinea pig skin as well as bovine cornea, aorta, and myocardium. Multiple pulses can lead to increased damage. However, a systematic decrease in damage with irradiance, predicted theoretically by an evaporation model of ablation, was not observed. The damage-zone thickness was approximately constant around the periphery of the cut, consistent with the existence of a liquid layer which stores heat and leads to tissue damage, and with a model of damage and ablation recently proposed by Zweig et al.

  11. Cellular and molecular effects for mutation induction in normal human cells irradiated with accelerated neon ions

    International Nuclear Information System (INIS)

    Suzuki, Masao; Tsuruoka, Chizuru; Kanai, Tatsuaki; Kato, Takeshi; Yatagai, Fumio; Watanabe, Masami

    2006-01-01

    We investigated the linear energy transfer (LET) dependence of mutation induction on the hypoxanthine-guanine phosphoribosyl transferase (HPRT) locus in normal human fibroblast-like cells irradiated with accelerated neon-ion beams. The cells were irradiated with neon-ion beams at various LETs ranging from 63 to 335 keV/μm. Neon-ion beams were accelerated by the Riken Ring Cyclotron at the Institute of Physical and Chemical Research in Japan. Mutation induction at the HPRT locus was detected to measure 6-thioguanine-resistant clones. The mutation spectrum of the deletion pattern of exons of mutants was analyzed using the multiplex polymerase chain reaction (PCR). The dose-response curves increased steeply up to 0.5 Gy and leveled off or decreased between 0.5 and 1.0 Gy, compared to the response to 137 Cs γ-rays. The mutation frequency increased up to 105 keV/μm and then there was a downward trend with increasing LET values. The deletion pattern of exons was non-specific. About 75-100% of the mutants produced using LETs ranging from 63 to 335 keV/μm showed all or partial deletions of exons, while among γ-ray-induced mutants 30% showed no deletions, 30% partial deletions and 40% complete deletions. These results suggested that the dose-response curves of neon-ion-induced mutations were dependent upon LET values, but the deletion pattern of DNA was not

  12. A methodology for the stochastic generation of hourly synthetic direct normal irradiation time series

    Science.gov (United States)

    Larrañeta, M.; Moreno-Tejera, S.; Lillo-Bravo, I.; Silva-Pérez, M. A.

    2018-02-01

    Many of the available solar radiation databases only provide global horizontal irradiance (GHI) while there is a growing need of extensive databases of direct normal radiation (DNI) mainly for the development of concentrated solar power and concentrated photovoltaic technologies. In the present work, we propose a methodology for the generation of synthetic DNI hourly data from the hourly average GHI values by dividing the irradiance into a deterministic and stochastic component intending to emulate the dynamics of the solar radiation. The deterministic component is modeled through a simple classical model. The stochastic component is fitted to measured data in order to maintain the consistency of the synthetic data with the state of the sky, generating statistically significant DNI data with a cumulative frequency distribution very similar to the measured data. The adaptation and application of the model to the location of Seville shows significant improvements in terms of frequency distribution over the classical models. The proposed methodology applied to other locations with different climatological characteristics better results than the classical models in terms of frequency distribution reaching a reduction of the 50% in the Finkelstein-Schafer (FS) and Kolmogorov-Smirnov test integral (KSI) statistics.

  13. Growth of normal or irradiated vaginal epithelium in in vivo cultures

    International Nuclear Information System (INIS)

    Tileva, M.

    1975-01-01

    Growth of normal or irradiated vaginal epithelium was studied by the method of F.M.Lazarenko (1959). Pieces of vaginal mucosa from immature albino rats, normal or exposed to 1000 or 2000 R, were embedded in celloidin and implanted into the abdominal wall of female immature rats. Implants were recovered for histological examinations from day 1 to day 10 after surgery. At day 1 post implantation, vaginal epithelium was found to have dedifferentiated. Cells showed a high mitotic index (MI = 16.2%). Cell proliferation progressed further to attain a peak rate at 3 days (MI = 32.7%). At 5 days, newly formed structures began to differentiate, and concurrently manifested a gradual decrease in cell proliferative activity (at 10 days, MI = 15.6%). Following exposure to 1000 R, vaginal epithelium displayed a similar pattern of growth and differentiation, the only difference from non-irradiated epithelium being that there was a transient mitotic delay over the first 3 days; mitotic rates reached a peak at 5 days (MI = 47.0%), were still high at 7 days (MI = 31.3%), and fell to 19% at 10 days. With this longer proliferation period, newly formed structures appeared ''luxuriant''. After a dose of 2000 R, vaginal epithelium failed to show any signs of growth at all investigated time intervals. These data are in agreement with evidence obtained by K.M.Svetikova (1961) and L.I.Chekulaeva (1969, 1974) for a good restitutional ability of epithelia of epidermal origin following exposure to 1200 R X-rays. By Warren' rule (1944), i.e., that cells should be considered radiosensitive if severely damaged by less than 2500 R, vaginal epithelium cells may be designated as relatively susceptible to radiation. (author)

  14. Variability of individual normal tissue radiation sensitivity. An international empirical evaluation of endogenous and exogenous

    International Nuclear Information System (INIS)

    Zimmermann, J.S.; Kumpf, L.; Kimmig, B.

    1998-01-01

    Background: The variability of normal-tissue response is of major concern for radiation therapy. Multiple endogenous and exogenous factors are qualitatively known to alter the acute and late tissue response. Which of them are regarded most important by the European radiation oncologists and what is, empirically, their quantitative influence on the acute or late tissue tolerance? Methods: In August 1997, we sent a questionnaire to 255 European radiation oncology departments. Among others, the questionnaire asked for endogenous and exogenous factors modifying the tissue response to radiation therapy and their quantitative influence on the acute and late radiation morbidity (TD5/5). Fifty-five questionnaires (21.5%) were answered. Results: Empirically, the most important endogenous factors to modify the acute tissue tolerance are (a) metabolic/other diseases with macro- or microangiopathia (17 answers [a]/32% mean decrease of tissue tolerance), (b) collagen diseases (9 a/37%) and (c) immune diseases (5 a/53%). As endogenous response modifiers for the TD5/5 are recognized (a) metabolic or other diseases leading to marcro- or microangiopathia (15 a/31%), (b) collagen diseases (11 a/38%) and (c) immune diseases (2 a/50%). Inflammations from any reason are assumed to alter the acute tissue tolerance by (6 a/26%) and the TD5/5 by (10 a/24%). Exogenous modifiers of the acute tissue response mentioned are (a) smoking (34 a/44%), (b) alcohol (23 a/45%), (c) nutrition/diets (16 a/45%), (d) hygiene (9 a/26%) and (e) medical therapies (10 a/37%). Exogenous factors assumed to influence the TD5/5 are (a) smoking (22 a/40%), (b) alcohol (15 a/38%), (c) nutrition/diets (9 a/48%), (d) hygiene (5 a/34%) and (e) medical therapies (10 a/30%). Conclusions: Exogenous factors are regarded more important by number and extent on the acute and late tissue response than endogenous modifiers. Both may have an important influence on the individual expression of normal tissue response. (orig

  15. Expression of HIF-1{alpha} in irradiated tissue is altered by topical negative-pressure therapy

    Energy Technology Data Exchange (ETDEWEB)

    Grimm, A.; Stange, S.; Labanaris, A.; Horch, R.E. [Erlangen-Nuernberg Univ., Erlangen (Germany). Dept. of Plastic and Hand Surgery; Dimmler, A. [Erlangen-Nuernberg Univ., Erlangen (Germany). Dept. of Pathology; Sauer, R.; Grabenbauer, G. [Erlangen-Nuernberg Univ. (Germany). Dept. of Radiation Oncology

    2007-03-15

    Background and Purpose: Despite the enormous therapeutic potential of modern radiotherapy, common side effects such as radiation-induced wound healing disorders remain a well-known clinical phenomenon. Topical negative pressure therapy (TNP) is a novel tool to alleviate intraoperative, percutaneous irradiation or brachytherapy. Since TNP has been shown to positively influence the perfusion of chronic, poorly vascularized wounds, the authors applied this therapeutic method to irradiated wounds and investigated the effect on tissue oxygenation in irradiated tissue in five patients. Material and Methods: With informed patients' consent, samples prior to and 4 and 8 days after continuous TNP with -125 mmHg were obtained during routine wound debridements. Granulation tissue was stained with hematoxylin-eosin, and additionally with CD31, HIF-1{alpha} (hypoxia-inducible factor-1{alpha}), and D2-40 to detect blood vessels, measure indirect signs of hypoxia, and lymph vessel distribution within the pre- and post-TNP samples. Results: In this first series of experiments, a positive influence of TNP onto tissue oxygenation in radiation-induced wounds could be demonstrated. TNP led to a significant decrease of 53% HIF-1{alpha}-positive cell nuclei. At the same time, a slight reduction of CD31-stained capillaries was seen in comparison to samples before TNP. Immunostaining with D2-40 revealed an increased number of lymphatic vessels with distended lumina and an alteration of the parallel orientation within the post-TNP samples. Conclusion: This study is, to the authors' knowledge, the first report on a novel previously not described histological marker to demonstrate the effects of TNP on HIF-1{alpha} expression as an indirect marker of tissue oxygenation in irradiated wounds, as demonstrated by a reduction of HIF-1{alpha} concentration after TNP. Since this observation may be of significant value to develop possible new strategies to treat radiation-induced tissue

  16. Expression of HIF-1α in irradiated tissue is altered by topical negative-pressure therapy

    International Nuclear Information System (INIS)

    Grimm, A.; Stange, S.; Labanaris, A.; Horch, R.E.; Dimmler, A.; Sauer, R.; Grabenbauer, G.

    2007-01-01

    Background and Purpose: Despite the enormous therapeutic potential of modern radiotherapy, common side effects such as radiation-induced wound healing disorders remain a well-known clinical phenomenon. Topical negative pressure therapy (TNP) is a novel tool to alleviate intraoperative, percutaneous irradiation or brachytherapy. Since TNP has been shown to positively influence the perfusion of chronic, poorly vascularized wounds, the authors applied this therapeutic method to irradiated wounds and investigated the effect on tissue oxygenation in irradiated tissue in five patients. Material and Methods: With informed patients' consent, samples prior to and 4 and 8 days after continuous TNP with -125 mmHg were obtained during routine wound debridements. Granulation tissue was stained with hematoxylin-eosin, and additionally with CD31, HIF-1α (hypoxia-inducible factor-1α), and D2-40 to detect blood vessels, measure indirect signs of hypoxia, and lymph vessel distribution within the pre- and post-TNP samples. Results: In this first series of experiments, a positive influence of TNP onto tissue oxygenation in radiation-induced wounds could be demonstrated. TNP led to a significant decrease of 53% HIF-1α-positive cell nuclei. At the same time, a slight reduction of CD31-stained capillaries was seen in comparison to samples before TNP. Immunostaining with D2-40 revealed an increased number of lymphatic vessels with distended lumina and an alteration of the parallel orientation within the post-TNP samples. Conclusion: This study is, to the authors' knowledge, the first report on a novel previously not described histological marker to demonstrate the effects of TNP on HIF-1α expression as an indirect marker of tissue oxygenation in irradiated wounds, as demonstrated by a reduction of HIF-1α concentration after TNP. Since this observation may be of significant value to develop possible new strategies to treat radiation-induced tissue injury, further investigations of HIF

  17. Quantifying glucose permeability and enhanced light penetration in ex vivo human normal and cancerous esophagus tissues with optical coherence tomography

    International Nuclear Information System (INIS)

    Zhao, Q L; Guo, Z Y; Wei, H J; Guo, X; Zhong, H Q; Li, L Q; Si, J L; Yang, H Q; Xie, S S; Wu, G Y; Li, X Y

    2011-01-01

    We report our pilot results on quantification of glucose (G) diffusion permeability in human normal esophagus and ESCC tissues in vitro by using OCT technique. The permeability coefficient of 40% aqueous solution of G was found to be (1.74±0.04)×10 -5 cm/s in normal esophagus and (2.45±0.06)×10 -5 cm/s in ESCC tissues. The results from this study indicate that ESCC tissues had a higher permeability coefficient compared to normal esophageal tissues, and the light penetration depths gradually increase with the increase of applied topically with G time for the normal esophageal and ESCC tissues. The results indicate that the permeability coefficient of G in cancer tissues was 1.41-fold than that in normal tissues, and the light penetration depth for the ESCC tissues is significantly smaller than that of normal esophagus tissues in the same time range. These results demonstrate that the optical clearing of normal and cancer esophagus tissues are improved after application of G

  18. Quantifying glucose permeability and enhanced light penetration in ex vivo human normal and cancerous esophagus tissues with optical coherence tomography

    Science.gov (United States)

    Zhao, Q. L.; Si, J. L.; Guo, Z. Y.; Wei, H. J.; Yang, H. Q.; Wu, G. Y.; Xie, S. S.; Li, X. Y.; Guo, X.; Zhong, H. Q.; Li, L. Q.

    2011-01-01

    We report our pilot results on quantification of glucose (G) diffusion permeability in human normal esophagus and ESCC tissues in vitro by using OCT technique. The permeability coefficient of 40% aqueous solution of G was found to be (1.74±0.04)×10-5 cm/s in normal esophagus and (2.45±0.06)×10-5 cm/s in ESCC tissues. The results from this study indicate that ESCC tissues had a higher permeability coefficient compared to normal esophageal tissues, and the light penetration depths gradually increase with the increase of applied topically with G time for the normal esophageal and ESCC tissues. The results indicate that the permeability coefficient of G in cancer tissues was 1.41-fold than that in normal tissues, and the light penetration depth for the ESCC tissues is significantly smaller than that of normal esophagus tissues in the same time range. These results demonstrate that the optical clearing of normal and cancer esophagus tissues are improved after application of G.

  19. ALERT. Adverse late effects of cancer treatment. Vol. 2. Normal tissue specific sites and systems

    Energy Technology Data Exchange (ETDEWEB)

    Rubin, Philip; Constine, Louis S. [Univ. Rochester Medical Center, NY (United States). Dept. of Radiation Oncology; Marks, Lawrence B. (ed.) [Univ. North Carolina and Lineberger, Comprehensive Cancer Center, Chapel Hill, NC (United States). Dept. of Radiation Oncology

    2014-09-01

    Comprehensively documents potential late effects in all the normal tissue sites in the human body. Considers in detail the detection, diagnosis, management and prevention of effects and discusses prognostic outcomes. Clearly presents radiation risk factors and interactions with chemotherapy effects. Provides the most current evidence-based medicine for cancer care survivorship guidelines. The literature on the late effects of cancer treatment is widely scattered in different journals since all major organ systems are affected and management is based on a variety of medical and surgical treatments. The aim of ALERT - Adverse Late Effects of Cancer Treatment is to offer a coherent multidisciplinary approach to the care of cancer survivors. The central paradigm is that cytotoxic multimodal therapy results in a perpetual cascade of events that affects each major organ system differently and is expressed continually over time. Essentially, radiation and chemotherapy are intense biologic modifiers that allow for cancer cure and cancer survivorship but accelerate senescence of normal tissues and increase the incidence of age-related diseases and second malignant tumors. Volume 2 of this two-volume work comprehensively documents potential late effects in all the normal tissue anatomic sites in the human body. The detection, diagnosis, management and prevention of effects are all considered in detail, and prognostic outcomes are discussed. Radiation risk factors and interactions with chemotherapy effects are clearly presented. The text is accompanied by numerous supportive illustrations and tables.

  20. Pattern of somatostatin receptors expression in normal and bladder cancer tissue samples.

    Science.gov (United States)

    Karavitakis, Markos; Msaouel, Pavlos; Michalopoulos, Vassilis; Koutsilieris, Michael

    2014-06-01

    Known risks factors for bladder cancer progression and recurrence are limited regarding their prognostic ability. Therefore identification of molecular determinants of disease progression could provide with more specific prognostic information and could be translated into new approaches for biomarker development. In the present study we evaluated, the expression patterns of somatostatin receptors 1-5 (SSTRs) in normal and tumor bladder tissues. The expression of SSTR1-5 was characterized in 45 normal and bladder cancer tissue samples using reverse transcriptase-polymerase chain reaction (RT-PCR). SSTR1 was expressed in 24 samples, SSTR2 in 15, SSTR3 in 23, SSTR4 in 16 and SSTR5 in all but one sample. Bladder cancer tissue samples expressed lower levels of SSTR3. Co-expression of SSTRs was associated with superficial disease. Our results demonstrate, for the first time, that there is expression of SSTR in normal and bladder cancer urothelium. Further studies are required to evaluate the prognostic and therapeutic significance of these findings. Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  1. Elemental analysis of the frontal lobe of 'normal' brain tissue and that affected by Alzheimer's disease

    International Nuclear Information System (INIS)

    Stedman, J.D.; Spyrou, N.M.

    1997-01-01

    'Normal' brain tissue and brain tissue affected by Alzheimer's disease has been taken from the frontal lobe of both hemispheres and their elemental compositions in terms of major, minor and trace elements compared. Brain samples were obtained from the MRC Alzheimer's Disease Brain Bank, London. 25 samples were taken from 18 individuals (5 males and 13 females) of mean age 79.9 ± 7.3 years with pathologically confirmed Alzheimer's disease and 26 samples from 15 individuals (8 males and 7 females) of mean age 71.8 ± 13.0 years with no pathological sings of Alzheimer's disease ('normals'). The elemental concentration of the samples were determined by the techniques of Rutherford backscattering (RBS) analysis, particle induced X-ray emission (PIXE) analysis and instrumental neutron activation analysis (INAA). Na, Mg, Al, Cl, K, Sc, Fe, Zn, Se, Br, Rb and Cs were detected by INAA and significant differences in concentrations were found between concentrations in normal and Alzheimer tissue for the elements. Na, Cl, K, Se, Br and Rb, P, S, Cl, K, Ca, Fe, Zn and Cd were detected by PIXE analysis and significant differences found for the elements P, S, Cl, K and Ca. (author)

  2. Evaluation of radio-protective effect of melatonin on whole body irradiation induced liver tissue damage.

    Science.gov (United States)

    Shirazi, Alireza; Mihandoost, Ehsan; Ghobadi, Ghazale; Mohseni, Mehran; Ghazi-Khansari, Mahmoud

    2013-01-01

    Ionizing radiation interacts with biological systems to induce excessive fluxes of free radicals that attack various cellular components. Melatonin has been shown to be a direct free radical scavenger and indirect antioxidant via its stimulatory actions on the antioxidant system.The aim of this study was to evaluate the antioxidant role of melatonin against radiation-induced oxidative injury to the rat liver after whole body irradiation. In this experimental study,thirty-two rats were divided into four groups. Group 1 was the control group, group 2 only received melatonin (30 mg/kg on the first day and 30 mg/kg on the following days), group 3 only received whole body gamma irradiation of 10 Gy, and group 4 received 30 mg/kg melatonin 30 minutes prior to radiation plus whole body irradiation of 10 Gy plus 30 mg/kg melatonin daily through intraperitoneal (IP) injection for three days after irradiation. Three days after irradiation, all rats were sacrificed and their livers were excised to measure the biochemical parameters malondialdehyde (MDA) and glutathione (GSH). Each data point represents mean ± standard error on the mean (SEM) of at least eight animals per group. A one-way analysis of variance (ANOVA) was performed to compare different groups, followed by Tukey's multiple comparison tests (p<0.05). The results demonstrated that whole body irradiation induced liver tissue damage by increasing MDA levels and decreasing GSH levels. Hepatic MDA levels in irradiated rats that were treated with melatonin (30 mg/kg) were significantly decreased, while GSH levels were significantly increased, when compared to either of the control groups or the melatonin only group. The data suggest that administration of melatonin before and after irradiation may reduce liver damage caused by gamma irradiation.

  3. Hole Burning Imaging Studies of Cancerous and Analogous Normal Ovarian Tissues Utilizing Organelle Specific Dyes

    Energy Technology Data Exchange (ETDEWEB)

    Matsuzaki, Satoshi [Iowa State Univ., Ames, IA (United States)

    2004-01-01

    Presented in this dissertation is the successful demonstration that nonphotochemical hole burning (NPWB) imaging can be used to study in vitro tissue cellular systems for discerning differences in cellular ultrastructures due to cancer development. This has been accomplished with the surgically removed cancerous ovarian and analogous normal peritoneal tissues from the same patient and the application of a fluorescent mitochondrion specific dye, Molecular Probe MitoFluor Far Red 680 (MF680), commonly known as rhodamine 800, that has been proven to exhibit efficient NPHB. From the results presented in Chapters 4 and 5 , and Appendix B, the following conclusions were made: (1) fluorescence excitation spectra of MF680 and confocal microscopy images of thin sliced tissues incubated with MF680 confirm the site-specificity of the probe molecules in the cellular systems. (2) Tunneling parameters, {lambda}{sub 0} and σΛ, as well as the standard hole burning parameters (namely, γ and S), have been determined for the tissue samples by hole growth kinetics (HGK) analyses. Unlike the preliminary cultured cell studies, these parameters have not shown the ability to distinguish tissue cellular matrices surrounding the chromophores. (3) Effects of an external electric (Stark) field on the nonphotochemical holes have been used to determine the changes in permanent dipole moment (fΔμ) for MF680 in tissue samples when burn laser polarization is parallel to the Stark field. Differences are detected between fΔμs in the two tissue samples, with the cancerous tissue exhibiting a more pronounced change (1.35-fold increase) in permanent dipole moment change relative to the normal analogs. It is speculated that the difference may be related to differences in mitochondrial membrane potentials in these tissue samples. (4) In the HGK mode, hole burning imaging (HBI) of cells adhered to coverslips and cooled to liquid helium temperatures in the complete absence of

  4. Patterns of proliferation and differentiation of irradiated haemopoietic stem cells cultured on normal 'stromal' cell colonies in vitro

    International Nuclear Information System (INIS)

    Mori, K.J.

    1981-01-01

    Experiments were designed to elucidate whether or not the irradiated bone marrow cells receive any stimulation for the self-replication and differentiation from normal 'stromal' cell colonies in the bone marrow cell culture in vitro. When irradiated or unirradiated bone marrow cells were overlaid on the normal adherent cell colonies, the proliferation of haemopoietic stem cells was supported, the degree of the stimulation depending on the starting cellular concentration. There was, however, no significant changes in the concentration of either CFUs or CFUc regardless of the dose of irradiation on the bone marrow cells overlaid. This was a great contrast to the dose-dependent decrease of CFUs or CFUc within the culture in which both the stem cells and stromal cells were simultaneously irradiated. These results suggest that the balance of self-replication and differentiation of the haemopoietic stem cells is affected only when haemopoietic microenvironment is perturbed. (author)

  5. N-isopropyl-p-iodoamphetamine receptors in normal and cancerous tissue of the human lung

    Energy Technology Data Exchange (ETDEWEB)

    Tanaka, Eiko; Mishima, Michiaki; Kawakami, Kenzo; Sakai, Naoki; Sugiura, Naoharu; Kuno, Kenshi [Kyoto Univ. (Japan). Dept. of Clinical Physiology; Taniguchi, Takashi [Kyoto Pharmaceutical Univ. (Japan). Dept. of Neurobiology

    1993-04-01

    N-Isopropyl-p-iodoamphetamine (IMP) receptors in normal human lung tissue were characterized using a radioligand binding assay with iodine-125 IMP as the ligand. Saturation binding studies revealed the presence of two binding sites with dissociation constant (K[sub d]) values of 53[+-]2 and 4687[+-]124 nM and maximum binding capacity (Bmax) values of 7[+-]1 and 133[+-]27 pmol/mg protein (n=5) respectively. The IC[sub 50] values of various amines were as follows: IMP, 9x10[sup -5] M; propranolol, 5x10[sup -4] M; haloperidol, 6x10[sup -4] M; ketamine, 9x10[sup -3] M; dopamine, 1x10[sup -2] M. The IMP receptors of cancerous tissue obtained from human lung also had two binding sites with K[sub d] values of 54[+-]2 and 5277[+-]652 nM and Bmax values of 7[+-]1 and 103[+-]21 pmol/mg protein (n=3) respectively. There was no significant difference in binding parameters between normal and cancerous lung tissue. These results demonstrate the existence of IMP receptors and suggest that cancer does not affect the nature of IMP receptors in human lung tissue. (orig.).

  6. Chemical evaluation of strawberry plants produced by tissue culturing of gamma irradiated seedlings

    International Nuclear Information System (INIS)

    Maraei, R.W.

    2007-01-01

    studies were conducted to evaluate the influence of gamma irradiation as a supplementary factor precedes tissue culture application on strawberry seedlings (c.v.Rosa Linda). the strawberry seedling were irradiated using 8 doses of co 60 gamma rays 50.75.100.125 ,150,250, 350 and 500 gray. tissue culture technique was applied on irradiated and unirradiated strawberry seedling. different characteristics of plantlets, plant and fruit of strawberry produced from the double treatment (irradiation followed by tissue culture) were studied as well as the early, total and exportable fruit yields. data indicated that, low radiation doses 50,75 and 100 gray increased all morphological and chemical characteristics of the plantlets, plant and fruit of strawberry, whereas radiation doses higher than 100 gray decreased them significantly. moreover 350 and gray were lethal doses. radiation dose 50 gray increased the survival percentage and the length of plantlets by 1.5% and 50% respectively more than the unirradiated treatment in all multiplication stages

  7. Antiandrogenic actions of medroxyprogesterone acetate on epithelial cells within normal human breast tissues cultured ex vivo.

    Science.gov (United States)

    Ochnik, Aleksandra M; Moore, Nicole L; Jankovic-Karasoulos, Tanja; Bianco-Miotto, Tina; Ryan, Natalie K; Thomas, Mervyn R; Birrell, Stephen N; Butler, Lisa M; Tilley, Wayne D; Hickey, Theresa E

    2014-01-01

    Medroxyprogesterone acetate (MPA), a component of combined estrogen-progestin therapy (EPT), has been associated with increased breast cancer risk in EPT users. MPA can bind to the androgen receptor (AR), and AR signaling inhibits cell growth in breast tissues. Therefore, the aim of this study was to investigate the potential of MPA to disrupt AR signaling in an ex vivo culture model of normal human breast tissue. Histologically normal breast tissues from women undergoing breast surgical operation were cultured in the presence or in the absence of the native AR ligand 5α-dihydrotestosterone (DHT), MPA, or the AR antagonist bicalutamide. Ki67, bromodeoxyuridine, B-cell CLL/lymphoma 2 (BCL2), AR, estrogen receptor α, and progesterone receptor were detected by immunohistochemistry. DHT inhibited the proliferation of breast epithelial cells in an AR-dependent manner within tissues from postmenopausal women, and MPA significantly antagonized this androgenic effect. These hormonal responses were not commonly observed in cultured tissues from premenopausal women. In tissues from postmenopausal women, DHT either induced or repressed BCL2 expression, and the antiandrogenic effect of MPA on BCL2 was variable. MPA significantly opposed the positive effect of DHT on AR stabilization, but these hormones had no significant effect on estrogen receptor α or progesterone receptor levels. In a subset of postmenopausal women, MPA exerts an antiandrogenic effect on breast epithelial cells that is associated with increased proliferation and destabilization of AR protein. This activity may contribute mechanistically to the increased risk of breast cancer in women taking MPA-containing EPT.

  8. Immunohistochemical Study of Expression of Sohlh1 and Sohlh2 in Normal Adult Human Tissues.

    Directory of Open Access Journals (Sweden)

    Xiaoli Zhang

    Full Text Available The expression pattern of Sohlh1 (spermatogenesis and oogenesis specific basic helix-loop-helix 1 and Sohlh2 in mice has been reported in previous studies. Sohlh1 and Sohlh2 are specifically expressed in spermatogonia, prespermatogonia in male mice and oocytes of primordial and primary follicles in female mice. In this report, we studied the expression pattern of Sohlh1 and Sohlh2 in human adult tissues. Immunohistochemical staining of Sohlh1 and Sohlh2 was performed in 5 samples of normal ovaries and testes, respectively. The results revealed that Sohlh genes are not only expressed in oocytes and spermatogonia, but also in granular cells, theca cells, Sertoli cells and Leydig cells, and in smooth muscles of blood vessel walls. To further investigate the expression of Sohlh genes in other adult human tissues, we collected representative normal adult tissues developed from three embryonic germ layers. Compared with the expression in mice, Sohlhs exhibited a much more extensive expression pattern in human tissues. Sohlhs were detected in testis, ovary and epithelia developed from embryonic endoderm, ectoderm and tissues developed from embryonic mesoderm. Sohlh signals were found in spermatogonia, Sertoli cells and also Leydig cells in testis, while in ovary, the expression was mainly in oocytes of primordial and primary follicles, granular cells and theca cells of secondary follicles. Compared with Sohlh2, the expression of Sohlh1 was stronger and more extensive. Our study explored the expression of Sohlh genes in human tissues and might provide insights for functional studies of Sohlh genes.

  9. Allograft tissue irradiation and failure rate after anterior cruciate ligament reconstruction: A systematic review.

    Science.gov (United States)

    Dashe, Jesse; Parisien, Robert L; Cusano, Antonio; Curry, Emily J; Bedi, Asheesh; Li, Xinning

    2016-06-18

    To evaluate whether anterior cruciate ligament (ACL) allograft irradiation is effective for sterility without compromising graft integrity and increasing failure rate. A literature search was conducted using PubMed, Cochrane, and Google. The following search terms were used: "Gamma irradiation AND anterior cruciate ligament AND allograft" with a return of 30 items. Filters used included: English language, years 1990-2015. There were 6 hits that were not reviewed, as there were only abstracts available. Another 5 hits were discarded, as they did not pertain to the topic of interest. There were 9 more articles that were excluded: Three studies were performed on animals and 6 studies were meta-analyses. Therefore, a total of 10 articles were applicable to review. There is a delicate dosing crossover where gamma irradiation is both effective for sterility without catastrophically compromising the structural integrity of the graft. Of note, low dose irradiation is considered less than 2.0 Mrad, moderate dose is between 2.1-2.4 Mrad, and high dose is greater than or equal to 2.5 Mrad. Based upon the results of the literature search, the optimal threshold for sterilization was found to be sterilization at less than 2.2 Mrad of gamma irradiation with the important caveat of being performed at low temperatures. The graft selection process also must include thorough donor screening and testing as well as harvesting the tissue in a sterile fashion. Utilization of higher dose (≥ 2.5 Mrad) of irradiation causes greater allograft tissue laxity that results in greater graft failure rate clinically in patients after ACL reconstruction. Allograft ACL graft gamma irradiated with less than 2.2 Mrad appears to be a reasonable alternative to autograft for patients above 25 years of age.

  10. Assessment of four shadow band correction models using beam normal irradiance data from the United Kingdom and Israel

    International Nuclear Information System (INIS)

    Lopez, G.; Muneer, T.; Claywell, R.

    2004-01-01

    Diffuse irradiance is a fundamental factor for all solar resource considerations. Diffuse irradiance is accurately determined by calculation from global and beam normal (direct) measurements. However, beam solar measurements and related support can be very expensive, and therefore, shadow bands are often used, along with pyranometers, to block the solar disk. The errors that result from the use of shadow bands are well known and have been studied by many authors. The thrust of this article is to examine four recognized techniques for correcting shadow band based, diffuse irradiance and statistically evaluate their individual performance using data culled from two contrasting sites within the United Kingdom and Israel

  11. Multi-time-scale heat transfer modeling of turbid tissues exposed to short-pulsed irradiations.

    Science.gov (United States)

    Kim, Kyunghan; Guo, Zhixiong

    2007-05-01

    A combined hyperbolic radiation and conduction heat transfer model is developed to simulate multi-time-scale heat transfer in turbid tissues exposed to short-pulsed irradiations. An initial temperature response of a tissue to an ultrashort pulse irradiation is analyzed by the volume-average method in combination with the transient discrete ordinates method for modeling the ultrafast radiation heat transfer. This response is found to reach pseudo steady state within 1 ns for the considered tissues. The single pulse result is then utilized to obtain the temperature response to pulse train irradiation at the microsecond/millisecond time scales. After that, the temperature field is predicted by the hyperbolic heat conduction model which is solved by the MacCormack's scheme with error terms correction. Finally, the hyperbolic conduction is compared with the traditional parabolic heat diffusion model. It is found that the maximum local temperatures are larger in the hyperbolic prediction than the parabolic prediction. In the modeled dermis tissue, a 7% non-dimensional temperature increase is found. After about 10 thermal relaxation times, thermal waves fade away and the predictions between the hyperbolic and parabolic models are consistent.

  12. The irradiation action on human dental tissue by X-rays and electrons. A nanoindenter study

    Energy Technology Data Exchange (ETDEWEB)

    Fraenzel, Wolfgang [Halle-Wittenberg Univ., Halle (Germany). Dept. of Physics; Gerlach, Reinhard [Halle-Wittenberg Univ., Halle (Germany). Clinic of Radiation Therapy

    2009-07-01

    It is known that ionizing radiation is used in medicine for Roentgen diagnostics and for radiation therapy. The radiation interacts with matter, in particular with biological one, essentially by scattering, photoelectric effect, Compton effect and pair production. To what extent the biological material is changed thereby, depends on the type and the amount of radiation energy, on the dose and on the tissue constitution. In modern radiation therapy two different kinds of radiation are used: high energy X-rays and electron radiation. In the case of head-neck tumors the general practice is an irradiation with high energy X-rays with absorbed dose to water up to 70 Gy. Teeth destruction has been identified as a side effect during irradiation. In addition, damage to the salivary glands is often observed which leads to a decrease or even the complete loss of the salivary secretion (xerostomia). This study shows how the different energy and radiation types damage the tooth tissue. The effects of both, high X-ray energy and high energy electrons, on the mechanical properties hardness and elasticity of the human dental tissue are measured by the nanoindentation technique. We compare these results with the effect of the irradiation of low X-ray energy on the dental tissue. (orig.)

  13. The irradiation action on human dental tissue by X-rays and electrons. A nanoindenter study

    International Nuclear Information System (INIS)

    Fraenzel, Wolfgang; Gerlach, Reinhard

    2009-01-01

    It is known that ionizing radiation is used in medicine for Roentgen diagnostics and for radiation therapy. The radiation interacts with matter, in particular with biological one, essentially by scattering, photoelectric effect, Compton effect and pair production. To what extent the biological material is changed thereby, depends on the type and the amount of radiation energy, on the dose and on the tissue constitution. In modern radiation therapy two different kinds of radiation are used: high energy X-rays and electron radiation. In the case of head-neck tumors the general practice is an irradiation with high energy X-rays with absorbed dose to water up to 70 Gy. Teeth destruction has been identified as a side effect during irradiation. In addition, damage to the salivary glands is often observed which leads to a decrease or even the complete loss of the salivary secretion (xerostomia). This study shows how the different energy and radiation types damage the tooth tissue. The effects of both, high X-ray energy and high energy electrons, on the mechanical properties hardness and elasticity of the human dental tissue are measured by the nanoindentation technique. We compare these results with the effect of the irradiation of low X-ray energy on the dental tissue. (orig.)

  14. Does Three-Dimensional External Beam Partial Breast Irradiation Spare Lung Tissue Compared With Standard Whole Breast Irradiation?

    International Nuclear Information System (INIS)

    Jain, Anudh K.; Vallow, Laura A.; Gale, Ashley A.; Buskirk, Steven J.

    2009-01-01

    Purpose: To determine whether three-dimensional conformal partial breast irradiation (3D-PBI) spares lung tissue compared with whole breast irradiation (WBI) and to include the biologically equivalent dose (BED) to account for differences in fractionation. Methods and Materials: Radiotherapy treatment plans were devised for WBI and 3D-PBI for 25 consecutive patients randomized on the NSABP B-39/RTOG 0413 protocol at Mayo Clinic in Jacksonville, Florida. WBI plans were for 50 Gy in 25 fractions, and 3D-PBI plans were for 38.5 Gy in 10 fractions. Volume of ipsilateral lung receiving 2.5, 5, 10, and 20 Gy was recorded for each plan. The linear quadratic equation was used to calculate the corresponding dose delivered in 10 fractions and volume of ipsilateral lung receiving these doses was recorded for PBI plans. Ipsilateral mean lung dose was recorded for each plan and converted to BED. Results: There was a significant decrease in volume of lung receiving 20 Gy with PBI (median, 4.4% vs. 7.5%; p 3 vs 4.85 Gy 3 , p = 0.07). PBI plans exposed more lung to 2.5 and 5 Gy. Conclusions: 3D-PBI exposes greater volumes of lung tissue to low doses of radiation and spares the amount of lung receiving higher doses when compared with WBI.

  15. Differentiating the two main histologic categories of fibroadenoma tissue from normal breast tissue by using multiphoton microscopy.

    Science.gov (United States)

    Nie, Y T; Wu, Y; Fu, F M; Lian, Y E; Zhuo, S M; Wang, C; Chen, J X

    2015-04-01

    Multiphoton microscopy has become a novel biological imaging technique that allows cellular and subcellular microstructure imaging based on two-photon excited fluorescence and second harmonic generation. In this work, we used multiphoton microscopy to obtain the high-contrast images of human normal breast tissue and two main histologic types of fibroadenoma (intracanalicular, pericanalicular). Moreover, quantitative image analysis was performed to characterize the changes of collagen morphology (collagen content, collagen orientation). The results show that multiphoton microscopy combined with quantitative method has the ability to identify the characteristics of fibroadenoma including changes of the duct architecture and collagen morphology in stroma. With the advancement of multiphoton microscopy, we believe that the technique has great potential to be a real-time histopathological diagnostic tool for intraoperative detection of fibroadenoma in the future. © 2015 The Authors Journal of Microscopy © 2015 Royal Microscopical Society.

  16. Iodine-131 dose dependent gene expression in thyroid cancers and corresponding normal tissues following the Chernobyl accident.

    Directory of Open Access Journals (Sweden)

    Michael Abend

    Full Text Available The strong and consistent relationship between irradiation at a young age and subsequent thyroid cancer provides an excellent model for studying radiation carcinogenesis in humans. We thus evaluated differential gene expression in thyroid tissue in relation to iodine-131 (I-131 doses received from the Chernobyl accident. Sixty three of 104 papillary thyroid cancers diagnosed between 1998 and 2008 in the Ukrainian-American cohort with individual I-131 thyroid dose estimates had paired RNA specimens from fresh frozen tumor (T and normal (N tissue provided by the Chernobyl Tissue Bank and satisfied quality control criteria. We first hybridized 32 randomly allocated RNA specimen pairs (T/N on 64 whole genome microarrays (Agilent, 4×44 K. Associations of differential gene expression (log(2(T/N with dose were assessed using Kruskall-Wallis and trend tests in linear mixed regression models. While none of the genes withstood correction for the false discovery rate, we selected 75 genes with a priori evidence or P kruskall/P trend <0.0005 for validation by qRT-PCR on the remaining 31 RNA specimen pairs (T/N. The qRT-PCR data were analyzed using linear mixed regression models that included radiation dose as a categorical or ordinal variable. Eleven of 75 qRT-PCR assayed genes (ACVR2A, AJAP1, CA12, CDK12, FAM38A, GALNT7, LMO3, MTA1, SLC19A1, SLC43A3, ZNF493 were confirmed to have a statistically significant differential dose-expression relationship. Our study is among the first to provide direct human data on long term differential gene expression in relation to individual I-131 doses and to identify a set of genes potentially important in radiation carcinogenesis.

  17. Changes in rat liver and adipose tissue lipogenesis after single lethal X-irradiation: modification by the restricted food intake

    International Nuclear Information System (INIS)

    Sedlakova, A.; Ahlers, I.; Praslicka, M.

    1981-01-01

    Male rats of Wistar strain were adapted during a 4-week period to the nutritional regimes of meal feeding (MF) and ad libitum (AL) and were irradiated with the single whole-body lethal X-ray dose 14.35 Gy after 22 h of fasting. Within the intervals 1, 24, 48 and 72 h after irradiation lipogenesis changes in the liver were studied by measuring 1- 14 C-acetate incorporation (74 KBq) in the total lipids, fatty acids and cholesterol, and in the white adipose tissue pieces by measuring U- 14 C-glucose incorporation (74 KBq) in the total lipids, fatty acids and glyceride glycerol. Lipogenesis increased in the liver of the irradiated rats as compared with sham irradiated rats and reached the maximal values at 72 h after irradiation in AL animals and at 48 h after irradiation in MF animals. Lipogenesis in the adipose tissue decreased in the irradiated rats as compared with the sham irradiated ones and continued to decrease with the post-irradiation period. The adaptation to the nutritional regime of meal feeding markedly modified lipogenesis in the liver and the adipose tissue of the irradiated rats. Long-term fasting (before and after irradiation) was supposed to be another modifying factor in the lipogenesis changes. Lipogenesis changes in the liver depended on the MF nutritional regime. (author)

  18. Changes in rat liver and adipose tissue lipogenesis after single lethal X-irradiation: modification by the restricted food intake

    Energy Technology Data Exchange (ETDEWEB)

    Sedlakova, A; Ahlers, I; Praslicka, M [Univerzita P.J. Safarika, Kosice (Czechoslovakia). Katedra Vseobecnej Biologie

    1981-01-01

    Male rats of Wistar strain were adapted during a 4-week period to the nutritional regimes of meal feeding (MF) and ad libitum (AL) and were irradiated with the single whole-body lethal X-ray dose 14.35 Gy after 22 h of fasting. Within the intervals 1, 24, 48 and 72 h after irradiation lipogenesis changes in the liver were studied by measuring 1-/sup 14/C-acetate incorporation (74 KBq) in the total lipids, fatty acids and cholesterol, and in the white adipose tissue pieces by measuring U-/sup 14/C-glucose incorporation (74 KBq) in the total lipids, fatty acids and glyceride glycerol. Lipogenesis increased in the liver of the irradiated rats as compared with sham irradiated rats and reached the maximal values at 72 h after irradiation in AL animals and at 48 h after irradiation in MF animals. Lipogenesis in the adipose tissue decreased in the irradiated rats as compared with the sham irradiated ones and continued to decrease with the post-irradiation period. The adaptation to the nutritional regime of meal feeding markedly modified lipogenesis in the liver and the adipose tissue of the irradiated rats. Long-term fasting (before and after irradiation) was supposed to be another modifying factor in the lipogenesis changes. Lipogenesis changes in the liver depended on the MF nutritional regime.

  19. Hypoxic regulation of cytoglobin and neuroglobin expression in human normal and tumor tissues

    Directory of Open Access Journals (Sweden)

    Emara Marwan

    2010-09-01

    Full Text Available Abstract Background Cytoglobin (Cygb and neuroglobin (Ngb are recently identified globin molecules that are expressed in vertebrate tissues. Upregulation of Cygb and Ngb under hypoxic and/or ischemic conditions in vitro and in vivo increases cell survival, suggesting possible protective roles through prevention of oxidative damage. We have previously shown that Ngb is expressed in human glioblastoma multiforme (GBM cell lines, and that expression of its transcript and protein can be significantly increased after exposure to physiologically relevant levels of hypoxia. In this study, we extended this work to determine whether Cygb is also expressed in GBM cells, and whether its expression is enhanced under hypoxic conditions. We also compared Cygb and Ngb expression in human primary tumor specimens, including brain tumors, as well as in human normal tissues. Immunoreactivity of carbonic anhydrase IX (CA IX, a hypoxia-inducible metalloenzyme that catalyzes the hydration of CO2 to bicarbonate, was used as an endogenous marker of hypoxia. Results Cygb transcript and protein were expressed in human GBM cells, and this expression was significantly increased in most cells following 48 h incubation under hypoxia. We also showed that Cygb and Ngb are expressed in both normal tissues and human primary cancers, including GBM. Among normal tissues, Cygb and Ngb expression was restricted to distinct cell types and was especially prominent in ductal cells. Additionally, certain normal organs (e.g. stomach fundus, small bowel showed distinct regional co-localization of Ngb, Cygb and CA IX. In most tumors, Ngb immunoreactivity was significantly greater than that of Cygb. In keeping with previous in vitro results, tumor regions that were positively stained for CA IX were also positive for Ngb and Cygb, suggesting that hypoxic upregulation of Ngb and Cygb also occurs in vivo. Conclusions Our finding of hypoxic up-regulation of Cygb/Ngb in GBM cell lines and human

  20. Normal tissue complications after radiation therapy Las complicaciones de la radioterapia en los tejidos sanos

    Directory of Open Access Journals (Sweden)

    Jolyon H. Hendry

    2006-09-01

    Full Text Available This paper describes the biological mechanisms of normal tissue reactions after radiation therapy, with reference to conventional treatments, new treatments, and treatments in developing countries. It also describes biological reasons for the latency period before tissue complications arise, the relationship of dose to incidence, the effect of increasing the size of the irradiated volume, early and late tissue reactions, effects of changes in dose fractionation and dose rate, and combined chemotherapy and radiotherapy responses. Examples are given of increases in knowledge of clinical radiobiology from trials of new protocols. Potential modification to treatments include the use of biological response modifiers. The introduction of "response prediction" modifications to treatments might also be available in the near future. Finally, the paper points out that in some radiotherapy centers, the biologically-effective doses prescribed for combined brachytherapy and teletherapy treatment of cervix cancer are lower than those prescribed in other centers. This issue needs to be addressed further. The wealth of preclinical and clinical data has led to a much greater understanding of the biological basis to radiotherapy. This understanding has underpinned a variety of new approaches in radiotherapy, including both physical and biological strategies. There is also the important issue of treatment of a large number of cancers in developing countries, for which efficacious resource-sparing protocols are being continuously developed. A unified scoring system should be widely accepted as the new standard in reporting the adverse effects of radiation therapy. Likewise, late toxicity should be reported on an actuarial basis as a mandatory endpoint.En este artículo se describen los mecanismos biológicos que intervienen en las reacciones provocadas por la radioterapia, tanto con tratamientos convencionales como con los más nuevos, y los aplicados en países en

  1. Outcomes of microvascular free tissue transfer in twice-irradiated patients.

    Science.gov (United States)

    Clancy, Kate; Melki, Sami; Awan, Musaddiq; Li, Shawn; Lavertu, Pierre; Fowler, Nicole; Yao, Min; Rezaee, Rod; Zender, Chad A

    2017-09-01

    Patients may require microvascular free tissue transfer (MFTT) following re-irradiation for recurrent cancer or radiation complications. The objective of this study was to describe the indications for and outcomes of free flaps performed in twice-radiated patients. A retrospective chart review identified the indications for and outcomes of 36 free flaps performed on 29 twice-irradiated patients. The free flap success rate was 92%. The most common indications requiring MFTT were cancer recurrence and osteoradionecrosis. Sixty-one percent experienced postoperative complications, most commonly wound infection (33%). Twenty-five percent of the procedures required return to the operating room due to postoperative complication. MFTT can be successfully performed in the twice-irradiated patient population with a success rate comparable to singly-radiated patients. Despite a high success rate, there is also a high rate of surgical site complications, especially infection. © 2017 Wiley Periodicals, Inc.

  2. Morphometric changes of pulmonary tissues after 20 Gy external irradiation of rat chest

    International Nuclear Information System (INIS)

    Cao Zhenshan; Ye Changqing; Yuan Lizhen

    1996-01-01

    The changes in the main parameters of the lungs at different periods of early stage after local 20 Gy external irradiation of the lungs were measured with morphometric method. The results indicated that the walls of pulmonary arterioles and venules thickened and the vascular permeability index (area of vascular lumen/total area of blood vessel) decreased 7 days after irradiation (P 2 , r = -0.919), indicating that narrowing of the vascular lumen was the result of thickening of the vascular wall. Fifteen days after irradiation, the pulmonary alveolar wall thickened, the area of alveolar cavity decreased and the area of pulmonary interstitial space increased (P<0.01). Electron microscopic examination demonstrated profuse exudation surrounding the microvessels, obvious evacuation of pulmonary type-II cells and increase in cellular types and quantity of pulmonary tissues

  3. Normal Values of Tissue-Muscle Perfusion Indexes of Lower Limbs Obtained with a Scintigraphic Method.

    Science.gov (United States)

    Manevska, Nevena; Stojanoski, Sinisa; Pop Gjorceva, Daniela; Todorovska, Lidija; Miladinova, Daniela; Zafirova, Beti

    2017-09-01

    Introduction Muscle perfusion is a physiologic process that can undergo quantitative assessment and thus define the range of normal values of perfusion indexes and perfusion reserve. The investigation of the microcirculation has a crucial role in determining the muscle perfusion. Materials and method The study included 30 examinees, 24-74 years of age, without a history of confirmed peripheral artery disease and all had normal findings on Doppler ultrasonography and pedo-brachial index of lower extremity (PBI). 99mTc-MIBI tissue muscle perfusion scintigraphy of lower limbs evaluates tissue perfusion in resting condition "rest study" and after workload "stress study", through quantitative parameters: Inter-extremity index (for both studies), left thigh/right thigh (LT/RT) left calf/right calf (LC/RC) and perfusion reserve (PR) for both thighs and calves. Results In our investigated group we assessed the normal values of quantitative parameters of perfusion indexes. Indexes ranged for LT/RT in rest study 0.91-1.05, in stress study 0.92-1.04. LC/RC in rest 0.93-1.07 and in stress study 0.93-1.09. The examinees older than 50 years had insignificantly lower perfusion reserve of these parameters compared with those younger than 50, LC (p=0.98), and RC (p=0.6). Conclusion This non-invasive scintigraphic method allows in individuals without peripheral artery disease to determine the range of normal values of muscle perfusion at rest and stress condition and to clinically implement them in evaluation of patients with peripheral artery disease for differentiating patients with normal from those with impaired lower limbs circulation.

  4. Binding of (/sup 3/H) progesterone to normal and neoplastic tissue samples from tumour bearing breasts

    Energy Technology Data Exchange (ETDEWEB)

    Pollow, K; Sinnecker, R; Schmidt-Gollwitzer, M; Boquoi, E; Pollow, B [Institut fuer Molekularbiologie und Biochemie, Frauenklinik Charlottenburg der Freien Universitat, Berlin (G.F.R.)

    1977-01-01

    Macromolecular components of normal human mammary cytosol (obtained from 'non-malignant tissue samples' from cancer bearing breasts) which bind (/sup 3/H)progesterone in vitro were characterized by sucrose gradient centrifugation, gel filtration on Agarose, ion exchange chromatography, isoelectric focusing, competition studies and kinetic parameters. The size of the cytoplasmic binding components vary with the concentration of KCl. In the absence of KCl, the major components are characterized by sedimentation coefficients of about 4 S and 8 S. In solutions containing 0.3M KCl, the cytoplasmic components sediment at 4 S in sucrose gradient. The corticosteroid-binding component of normal human mammary cytosol both sediment at about the same rate in the presence of 0.3M KCl and chromatograph as a single component on Agarose. The isoelectric point of the progesterone-binding component of normal human mammary cytosol was located around pH 5.0. The progesterone-binding component was more thermo-labile than serum CBG. CBG was inactivated at temperatures above 45 deg C but temperature above 20 deg C destroyed specific progesterone receptor binding. Progesterone receptor concentrations in normal mammary cytosol of premenopausal women depended on the menstrual cycle. The binding of progesterone was highest around the time of ovulation. In breast tumor tissue samples the progesterone receptor concentration was lower than in the normal mammary cytosol (obtained in each case from the same tumor-bearing breast). In 5 out of 37 breast tumor samples progesterone binding activity could not be detected.

  5. Characterization of adenoviral transduction profile in prostate cancer cells and normal prostate tissue.

    Science.gov (United States)

    Ai, Jianzhong; Tai, Phillip W L; Lu, Yi; Li, Jia; Ma, Hong; Su, Qin; Wei, Qiang; Li, Hong; Gao, Guangping

    2017-09-01

    Prostate diseases are common in males worldwide with high morbidity. Gene therapy is an attractive therapeutic strategy for prostate diseases, however, it is currently underdeveloped. As well known, adeno virus (Ad) is the most widely used gene therapy vector. The aims of this study are to explore transduction efficiency of Ad in prostate cancer cells and normal prostate tissue, thus further providing guidance for future prostate pathophysiological studies and therapeutic development of prostate diseases. We produced Ad expressing enhanced green fluorescence protein (EGFP), and characterized the transduction efficiency of Ad in both human and mouse prostate cancer cell lines in vitro, as well as prostate tumor xenograft, and wild-type mouse prostate tissue in vivo. Ad transduction efficiency was determined by EGFP fluorescence using microscopy and flow cytometry. Cell type-specific transduction was examined by immunofluorescence staining of cell markers. Our data showed that Ad efficiently transduced human and mouse prostate cancer cells in vitro in a dose dependent manner. Following intratumoral and intraprostate injection, Ad could efficiently transduce prostate tumor xenograft and the major prostatic cell types in vivo, respectively. Our findings suggest that Ad can efficiently transduce prostate tumor cells in vitro as well as xenograft and normal prostate tissue in vivo, and further indicate that Ad could be a potentially powerful toolbox for future gene therapy of prostate diseases. © 2017 Wiley Periodicals, Inc.

  6. Sarcoglycans in the normal and pathological breast tissue of humans: an immunohistochemical and molecular study.

    Science.gov (United States)

    Arco, Alba; Favaloro, Angelo; Gioffrè, Mara; Santoro, Giuseppe; Speciale, Francesco; Vermiglio, Giovanna; Cutroneo, Giuseppina

    2012-01-01

    The sarcoglycan complex, consisting of α-, β-, γ-, δ- and ε-sarcoglycans, is a multimember transmembrane system providing a mechanosignaling connection from the cytoskeleton to the extracellular matrix. Whereas the expression of α- and γ-sarcoglycan is restricted to striated muscle, other sarcoglycans are widely expressed. Although many studies have investigated sarcoglycans in all muscle types, insufficient data are available on the distribution of the sarcoglycan complex in nonmuscle tissue. On this basis, we used immunohistochemical and RT-PCR techniques to study preliminarily the sarcoglycans in normal glandular breast tissue (which has never been studied in the literature on these proteins) to verify the effective wider distribution of this complex. Moreover, to understand the role of sarcoglycans, we also tested samples obtained from patients affected by fibrocystic mastopathy and breast fibroadenoma. Our data showed, for the first time, that all sarcoglycans are always detectable in all normal samples both in epithelial and myoepithelial cells; in pathological breast tissue, all sarcoglycans appeared severely reduced. These data demonstrated that all sarcoglycans, not only β-, δ-, and ε-sarcoglycans, have a wider distribution, implying a new unknown role for these proteins. Moreover, in breast diseases, sarcoglycans containing cadherin domain homologs could provoke a loss of strong adhesion between epithelial cells, permitting and facilitating the degeneration of these benign breast tumors into malignant tumors. Consequently, sarcoglycans could play an important and intriguing role in many breast diseases and in particular in tumor progression from benign to malignant. Copyright © 2011 S. Karger AG, Basel.

  7. MO-D-BRF-01: Pediatric Treatment Planning II: The PENTEC Report On Normal Tissue Complications

    International Nuclear Information System (INIS)

    Constine, L; Hodgson, D; Bentzen, S

    2014-01-01

    With advances in multimodality therapy, childhood cancer cure rates approach 80%. However, both radiotherapy and chemotherapy may cause debilitating or even fatal ‘late effects’ that are critical to understand, mitigate, or prevent. QUANTEC identified the uncertainties relating to side-effects of adult treatments, but this is more complicated for children in whom a mosaic of tissues develops at different rates and temporal sequences. Childhood cancer survivors have long life expectancy and may develop treatmentinduced secondary cancers and severe organ/tissue injury decades after treatment. Collaborative long-term observational studies and clinical research programs for survivors of pediatric and adolescent cancer provide some dose-response data for follow-up periods exceeding 40 years. Data analysis is challenging due to the influence of both therapeutic and developmental variables. PENTEC is a group of radiation oncologists, pediatric oncologists, subsepcialty physicians, medical physicists, biomathematic modelers/statisticians, and epidemiologists charged with conducting a critical synthesis of existing literature aiming to: critically analyze radiation dose-volume effects on normal tissue tolerances as a function of age/development in pediatric cancer patients in order to inform treatment planning and improve outcomes for survivors; describe relevant physics issues specific to pediatric radiotherapy; propose dose-volumeoutcome reporting standards to improve the knowledge base to inform future treatment guidelines. PENTEC has developed guidelines for systematic literature reviews, data extraction tolls and data analysis. This education session will discuss:1. Special considerations for normal tissue radiation response of children/adolescents, e.g. the interplay between development and radiotherapy effects.2. Epidemiology of organ/tissue injuries and secondary cancers.3. Exploration of dose-response differences between children and adults4. Methodology for

  8. MO-D-BRF-01: Pediatric Treatment Planning II: The PENTEC Report On Normal Tissue Complications

    Energy Technology Data Exchange (ETDEWEB)

    Constine, L; Hodgson, D; Bentzen, S [University of Maryland, Baltimore, MD (United States)

    2014-06-15

    With advances in multimodality therapy, childhood cancer cure rates approach 80%. However, both radiotherapy and chemotherapy may cause debilitating or even fatal ‘late effects’ that are critical to understand, mitigate, or prevent. QUANTEC identified the uncertainties relating to side-effects of adult treatments, but this is more complicated for children in whom a mosaic of tissues develops at different rates and temporal sequences. Childhood cancer survivors have long life expectancy and may develop treatmentinduced secondary cancers and severe organ/tissue injury decades after treatment. Collaborative long-term observational studies and clinical research programs for survivors of pediatric and adolescent cancer provide some dose-response data for follow-up periods exceeding 40 years. Data analysis is challenging due to the influence of both therapeutic and developmental variables. PENTEC is a group of radiation oncologists, pediatric oncologists, subsepcialty physicians, medical physicists, biomathematic modelers/statisticians, and epidemiologists charged with conducting a critical synthesis of existing literature aiming to: critically analyze radiation dose-volume effects on normal tissue tolerances as a function of age/development in pediatric cancer patients in order to inform treatment planning and improve outcomes for survivors; describe relevant physics issues specific to pediatric radiotherapy; propose dose-volumeoutcome reporting standards to improve the knowledge base to inform future treatment guidelines. PENTEC has developed guidelines for systematic literature reviews, data extraction tolls and data analysis. This education session will discuss:1. Special considerations for normal tissue radiation response of children/adolescents, e.g. the interplay between development and radiotherapy effects.2. Epidemiology of organ/tissue injuries and secondary cancers.3. Exploration of dose-response differences between children and adults4. Methodology for

  9. An automatic method to discriminate malignant masses from normal tissue in digital mammograms

    International Nuclear Information System (INIS)

    Brake, Guido M. te; Karssemeijer, Nico; Hendriks, Jan H.C.L.

    2000-01-01

    Specificity levels of automatic mass detection methods in mammography are generally rather low, because suspicious looking normal tissue is often hard to discriminate from real malignant masses. In this work a number of features were defined that are related to image characteristics that radiologists use to discriminate real lesions from normal tissue. An artificial neural network was used to map the computed features to a measure of suspiciousness for each region that was found suspicious by a mass detection method. Two data sets were used to test the method. The first set of 72 malignant cases (132 films) was a consecutive series taken from the Nijmegen screening programme, 208 normal films were added to improve the estimation of the specificity of the method. The second set was part of the new DDSM data set from the University of South Florida. A total of 193 cases (772 films) with 372 annotated malignancies was used. The measure of suspiciousness that was computed using the image characteristics was successful in discriminating tumours from false positive detections. Approximately 75% of all cancers were detected in at least one view at a specificity level of 0.1 false positive per image. (author)

  10. Pattern of Bone Generation after Irradiation in Vascularized Tissue Engineered Constructs.

    Science.gov (United States)

    Eweida, Ahmad; Fathi, Ibrahim; Eltawila, Ahmed M; Elsherif, Ahmad M; Elkerm, Yasser; Harhaus, Leila; Kneser, Ulrich; Sakr, Mahmoud F

    2018-02-01

     Regenerative medicine modalities provide promising alternatives to conventional reconstruction techniques but are still deficient after malignant tumor excision or irradiation due to defective vascularization.  We investigated the pattern of bone formation in axially vascularized tissue engineering constructs (AVTECs) after irradiation in a study that mimics the clinical scenario after head and neck cancer. Heterotopic bone generation was induced in a subcutaneously implanted AVTEC in the thigh of six male New Zealand rabbits. The tissue construct was made up of Nanobone (Artoss GmbH; Rostock, Germany) granules mixed with autogenous bone marrow and 80 μL of bone morphogenic protein-2 at a concentration of 1.5 μg/μL. An arteriovenous loop was created microsurgically between the saphenous vessels and implanted in the core of the construct to induce axial vascularization. The constructs were subjected to external beam irradiation on postoperative day 20 with a single dose of 15 Gy. The constructs were removed 20 days after irradiation and subjected to histological and immunohistochemical analysis for vascularization, bone formation, apoptosis, and cellular proliferation.  The vascularized constructs showed homogenous vascularization and bone formation both in their central and peripheral regions. Although vascularity, proliferation, and apoptosis were similar between central and peripheral regions of the constructs, significantly more bone was formed in the central regions of the constructs.  The study shows for the first time the pattern of bone formation in AVTECs after irradiation using doses comparable to those applied after head and neck cancer. Axial vascularization probably enhances the osteoinductive properties in the central regions of AVTECs after irradiation. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  11. Detection of free radicals in γ-irradiated seasnail hard tissues by electron paramagnetic resonance

    International Nuclear Information System (INIS)

    Koeseoglu, Rahmi; Koeksal, Fevzi

    2003-01-01

    Gamma-irradiated seasnail (from family of Helix lukortium) hard tissues (CaCO 3 ) were investigated by electron paramagnetic resonance (EPR) at room temperature. The radicals produced by γ-irradiation in seasnail were attributed to orthorhombic C · O 2 - , freely rotating C · O 2 - , orthorhombic C · O 3 - , axial C · O 3 - , and axial C · O 3 3- free radicals. Unirradiated seasnail hard tissues also feature Mn 2+ ions in their EPR spectra. The hyperfine values were determined for the 13 C nucleus in the orthorhombic C · O 2 - and axial C · O 3 3- free radicals and for the manganese impurity ions. The g values of all the free radicals have been measured. The results were compared with the literature data for similar defects

  12. Effect of propolis feeding on rat tissues damaged by X-ray irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Ji Hoon; Seo, Eul Won [Andong National Univ., Andong (Korea, Republic of); Ji, Tae Jeong [Kaya Univ., Goryeong (Korea, Republic of)

    2007-06-15

    Present study aimed to investigate the radioprotective effects of propolis feeding on rat tissues damaged by X-ray irradiation. It was shown that the number of white blood cell in X-ray irradiated group supplemented with propolis increased as much to those of the control group and also the GOT activities among the blood components were decreased after propolis feeding. The mineral contents such as Mg, Fe, Ca, Mn, Cu, Mo, Ni, As in liver were increased as compared with those of the control group but maintained lower level than those of only irradiated groups, implying that the propolis feeding elevated the recovery capability of white blood cell effectively and propolis have a potential resistance to cell damage by X-ray. According to histological observations of the testis, intestine and liver tissues which are irradiated after feeding propolis, the numbers of damaged undifferentiated cells were decreased in testis and the shape of the goblet cells and inner and outer muscular layers in intestine were restored to the original state and the hepatocytes and interlobular veins were shown intact in liver, suggesting that propolis has a potential capacity to restore cell shapes or resist deformation of cell.

  13. Effects of tissue inhomogeneities on dose patterns in cylinders irradiated by negative pion beams

    International Nuclear Information System (INIS)

    Hamm, R.N.; Wright, H.A.; Turner, J.E.

    1975-10-01

    Effects of the presence of inhomogeneities in tissue irradiated by negative pion beams are investigated. Soft-tissue targets are considered with embedded regions of bone and cavities of air. The absorbed dose is calculated as a function of position in the targets for parallel and converging beams and for two parallel beams that enter the target from opposite sides. Isodose contours are calculated and displayed in each case. While these studies show expected trends, they indicate that specific calculations are needed for other beam parameters and target geometries. The contributions of neutrons to the dose contours can be seen from several calculations made both with and without neutrons

  14. Improvement of potato tolerance to salinity using tissue culture techniques and irradiation with in vitro selection

    International Nuclear Information System (INIS)

    Al-Safadi, B.; Arabi, M. I. E.

    2006-01-01

    A mutation breeding program was conducted to improve potato (Solanum tuberosum) tolerance to salinity. In vitro cultured explants from potato cvs. Draga, Diamant, Spunta were irradiated with gamma doses 25, 30, and 35 Gy. Mutants were isolated to get rid of chimeral tissues and subsequently propagated for in vitro and pot selection pressure. Cultivar Sponta produced the highest number of tolerant plants (4) and only one plant was obtained from Diamant. (authors)

  15. Post-radiation changes in oral tissues - An analysis of cancer irradiation cases

    Directory of Open Access Journals (Sweden)

    Jay Ashokkumar Pandya

    2014-01-01

    Full Text Available Introduction: Radiation, commonly employed as neoadjuvant, primary, and adjuvant therapy for head and neck cancer causes numerous epithelial and stromal changes, prominent among which is fibrosis with its early and late consequences. Very little is known about the true nature of the fibrosed tissue and the type of fibers accumulated. Radiotherapy affects the supporting tumor stroma often resulting in a worsening grade of tumor post-radiation. Aim: To study epithelial, neoplastic, stromal, and glandular changes in oral cavity induced by radiation therapy for oral squamous cell carcinoma (OSCC using special stains. Materials and Methods: The study included 27 samples of recurrent OSCC following completion of radiotherapy (recurrence within an average span of 11 months, and 26 non-irradiated cases of OSCC. Patients with a history of combined radiotherapy and chemotherapy were not included in the study. The epithelial changes assessed included epithelial atrophy, apoptosis, necrosis, dysplasia, and neoplasia. The connective tissue was evaluated for amount of fibrosis, quality of fibers (using picrosirius red staining, fibrinous exudate, necrosis, pattern of invasion, vessel wall thickening, and salivary gland changes. The aforementioned changes were assessed using light and polarizing microscopy and tabulated. Statistical Analysis: Epithelial and connective tissue parameters were compared between the irradiated and non-irradiated cases using chi square and t-tests. Results: Epithelial and connective tissue parameters were found to be increased in irradiated patients. Pattern of invasion by tumor cells varied from strands and  cords between the two groups studied. The effect of radiation was seen to reflect on the maturity of fibers and the regularity of their distribution.

  16. Nonlinear optical microscopy for histology of fresh normal and cancerous pancreatic tissues.

    Directory of Open Access Journals (Sweden)

    Wenyan Hu

    Full Text Available BACKGROUND: Pancreatic cancer is a lethal disease with a 5-year survival rate of only 1-5%. The acceleration of intraoperative histological examination would be beneficial for better management of pancreatic cancer, suggesting an improved survival. Nonlinear optical methods based on two-photon excited fluorescence (TPEF and second harmonic generation (SHG of intrinsic optical biomarkers show the ability to visualize the morphology of fresh tissues associated with histology, which is promising for real-time intraoperative evaluation of pancreatic cancer. METHODOLOGY/PRINCIPAL FINDINGS: In order to investigate whether the nonlinear optical imaging methods have the ability to characterize pancreatic histology at cellular resolution, we studied different types of pancreatic tissues by using label-free TPEF and SHG. Compared with other routine methods for the preparation of specimens, fresh tissues without processing were found to be most suitable for nonlinear optical imaging of pancreatic tissues. The detailed morphology of the normal rat pancreas was observed and related with the standard histological images. Comparatively speaking, the preliminary images of a small number of chemical-induced pancreatic cancer tissues showed visible neoplastic differences in the morphology of cells and extracellular matrix. The subcutaneous pancreatic tumor xenografts were further observed using the nonlinear optical microscopy, showing that most cells are leucocytes at 5 days after implantation, the tumor cells begin to proliferate at 10 days after implantation, and the extracellular collagen fibers become disordered as the xenografts grow. CONCLUSIONS/SIGNIFICANCE: In this study, nonlinear optical imaging was used to characterize the morphological details of fresh pancreatic tissues for the first time. We demonstrate that it is possible to provide real-time histological evaluation of pancreatic cancer by the nonlinear optical methods, which present an

  17. Assessment of ANN and SVM models for estimating normal direct irradiation (H_b)

    International Nuclear Information System (INIS)

    Santos, Cícero Manoel dos; Escobedo, João Francisco; Teramoto, Érico Tadao; Modenese Gorla da Silva, Silvia Helena

    2016-01-01

    Highlights: • The performance of SVM and ANN in estimating Normal Direct Irradiation (H_b) was evaluated. • 12 models using different input variables are developed (hourly and daily partitions). • The most relevant input variables for DNI are kt, H_s_c and insolation ratio (r′ = n/N). • Support Vector Machine (SVM) provides accurate estimates and outperforms the Artificial Neural Network (ANN). - Abstract: This study evaluates the estimation of hourly and daily normal direct irradiation (H_b) using machine learning techniques (ML): Artificial Neural Network (ANN) and Support Vector Machine (SVM). Time series of different meteorological variables measured over thirteen years in Botucatu were used for training and validating ANN and SVM. Seven different sets of input variables were tested and evaluated, which were chosen based on statistical models reported in the literature. Relative Mean Bias Error (rMBE), Relative Root Mean Square Error (rRMSE), determination coefficient (R"2) and “d” Willmott index were used to evaluate ANN and SVM models. When compared to statistical models which use the same set of input variables (R"2 between 0.22 and 0.78), ANN and SVM show higher values of R"2 (hourly models between 0.52 and 0.88; daily models between 0.42 and 0.91). Considering the input variables, atmospheric transmissivity of global radiation (kt), integrated solar constant (H_s_c) and insolation ratio (n/N, n is sunshine duration and N is photoperiod) were the most relevant in ANN and SVM models. The rMBE and rRMSE values in the two time partitions of SVM models are lower than those obtained with ANN. Hourly ANN and SVM models have higher rRMSE values than daily models. Optimal performance with hourly models was obtained with ANN4"h (rMBE = 12.24%, rRMSE = 23.99% and “d” = 0.96) and SVM4"h (rMBE = 1.75%, rRMSE = 20.10% and “d” = 0.96). Optimal performance with daily models was obtained with ANN2"d (rMBE = −3.09%, rRMSE = 18.95% and “d” = 0

  18. High-risk human papilloma virus in archival tissues of oral pathosis and normal oral mucosa

    Directory of Open Access Journals (Sweden)

    Raghu Dhanapal

    2015-01-01

    Full Text Available Objectives: Oral cancer ranks third among all cancers in the Indian population. Human papilloma virus (HPV plays a significant role in oral carcinogenesis. Population-based subtype variations are present in the HPV prevalence. This study gives an emphasis on the parameters to be considered in formalin fixed paraffin embedded tissues for polymerase chain reaction (PCR-based research work. Materials and Methods: Cross-sectional study on archival paraffin-embedded tissue samples of oral squamous cell carcinoma (OSCC, epithelial dysplasia, and normal oral mucosa surrounding impacted tooth was amplified by PCR for the E6 gene of HPV type 16 and E1 gene of HPV type 18. Results: HPV 18 was positive in three OSCC cases. There was no statistically significant association of the positivity of HPV with the age, gender or habit. The HPV positive patients had a tobacco habit and were of a younger age group. Conclusion: The presence of HPV in carcinomatous tissue highlights the possible role of HPV in carcinogenesis and archival paraffin embedded tissue specimen can be used for this analysis. Recent studies on genomic analyses have highlighted that the HPV positive tumors are a separate subgroup based on genomic sequencing. The results of a larger retrospective study will help further in our understanding of the role of HPV in carcinogenesis, this study could form the baseline for such follow-up studies.

  19. High-risk human papilloma virus in archival tissues of oral pathosis and normal oral mucosa.

    Science.gov (United States)

    Dhanapal, Raghu; Ranganathan, K; Kondaiah, Paturu; Devi, R Uma; Joshua, Elizabeth; Saraswathi, T R

    2015-01-01

    Oral cancer ranks third among all cancers in the Indian population. Human papilloma virus (HPV) plays a significant role in oral carcinogenesis. Population-based subtype variations are present in the HPV prevalence. This study gives an emphasis on the parameters to be considered in formalin fixed paraffin embedded tissues for polymerase chain reaction (PCR)-based research work. Cross-sectional study on archival paraffin-embedded tissue samples of oral squamous cell carcinoma (OSCC), epithelial dysplasia, and normal oral mucosa surrounding impacted tooth was amplified by PCR for the E6 gene of HPV type 16 and E1 gene of HPV type 18. HPV 18 was positive in three OSCC cases. There was no statistically significant association of the positivity of HPV with the age, gender or habit. The HPV positive patients had a tobacco habit and were of a younger age group. The presence of HPV in carcinomatous tissue highlights the possible role of HPV in carcinogenesis and archival paraffin embedded tissue specimen can be used for this analysis. Recent studies on genomic analyses have highlighted that the HPV positive tumors are a separate subgroup based on genomic sequencing. The results of a larger retrospective study will help further in our understanding of the role of HPV in carcinogenesis, this study could form the baseline for such follow-up studies.

  20. YAP expression in normal and neoplastic breast tissue: an immunohistochemical study.

    Science.gov (United States)

    Jaramillo-Rodríguez, Yolanda; Cerda-Flores, Ricardo M; Ruiz-Ramos, Ruben; López-Márquez, Francisco C; Calderón-Garcidueñas, Ana Laura

    2014-04-01

    Yes-associated protein (YAP) is a transcriptional factor involved in normal cell proliferation, apoptosis and carcinogenesis; however, its contribution to breast cancer (BC) is still controversial. We undertook this study to compare the expression of YAP by immunohistochemistry (IHC) in normal breast tissue of women without breast cancer (BC) (controls), non-neoplastic breast tissue in women with cancer (internal controls) and in four different subtypes of invasive ductal carcinoma. There were 17 controls and 105 tumor cases (53 luminal A, 15 luminal B, 20 overexpression of HER2 and 17 triple negative cases) studied by IHC. Statistical analysis included χ(2) for linear trend (Extended Mantel-Haenszel). There were 40% of internal controls that showed expression of YAP in myoepithelial cells, whereas in controls expression was 100%. In controls, 3/17 (17.6%) showed cytoplasmic staining in luminal cells. There was a significant difference in nuclear expression between the ductal BC subtypes. Luminal A had 4% of positive cases with <10% of cells affected in each case; in contrast, there were 17-20% of positive cases in the other groups with 50% or more of stained cells. YAP expression in stromal cells was not observed in controls or in triple-negative cases, and luminal B pattern had the highest YAP nuclear expression (20%). YAP showed decreased expression in tumor cells compared with normal breast tissue. These findings are consistent with a role of YAP as a suppressor gene in BC and show differences in YAP expression in different patterns of ductal BC. Copyright © 2014 IMSS. Published by Elsevier Inc. All rights reserved.

  1. A System for Continual Quality Improvement of Normal Tissue Delineation for Radiation Therapy Treatment Planning

    Energy Technology Data Exchange (ETDEWEB)

    Breunig, Jennifer; Hernandez, Sophy; Lin, Jeffrey; Alsager, Stacy; Dumstorf, Christine; Price, Jennifer; Steber, Jennifer; Garza, Richard; Nagda, Suneel; Melian, Edward; Emami, Bahman [Department of Radiation Oncology, Loyola University Medical Center, Maywood, Illinois (United States); Roeske, John C., E-mail: jroeske@lumc.edu [Department of Radiation Oncology, Loyola University Medical Center, Maywood, Illinois (United States)

    2012-08-01

    Purpose: To implement the 'plan-do-check-act' (PDCA) cycle for the continual quality improvement of normal tissue contours used for radiation therapy treatment planning. Methods and Materials: The CT scans of patients treated for tumors of the brain, head and neck, thorax, pancreas and prostate were selected for this study. For each scan, a radiation oncologist and a diagnostic radiologist, outlined the normal tissues ('gold' contours) using Radiation Therapy Oncology Group (RTOG) guidelines. A total of 30 organs were delineated. Independently, 5 board-certified dosimetrists and 1 trainee then outlined the same organs. Metrics used to compare the agreement between the dosimetrists' contours and the gold contours included the Dice Similarity Coefficient (DSC), and a penalty function using distance to agreement. Based on these scores, dosimetrists were re-trained on those organs in which they did not receive a passing score, and they were subsequently re-tested. Results: Passing scores were achieved on 19 of 30 organs evaluated. These scores were correlated to organ volume. For organ volumes <8 cc, the average DSC was 0.61 vs organ volumes {>=}8 cc, for which the average DSC was 0.91 (P=.005). Normal tissues that had the lowest scores included the lenses, optic nerves, chiasm, cochlea, and esophagus. Of the 11 organs that were considered for re-testing, 10 showed improvement in the average score, and statistically significant improvement was noted in more than half of these organs after education and re-assessment. Conclusions: The results of this study indicate the feasibility of applying the PDCA cycle to assess competence in the delineation of individual organs, and to identify areas for improvement. With testing, guidance, and re-evaluation, contouring consistency can be obtained across multiple dosimetrists. Our expectation is that continual quality improvement using the PDCA approach will ensure more accurate treatments and dose

  2. A System for Continual Quality Improvement of Normal Tissue Delineation for Radiation Therapy Treatment Planning

    International Nuclear Information System (INIS)

    Breunig, Jennifer; Hernandez, Sophy; Lin, Jeffrey; Alsager, Stacy; Dumstorf, Christine; Price, Jennifer; Steber, Jennifer; Garza, Richard; Nagda, Suneel; Melian, Edward; Emami, Bahman; Roeske, John C.

    2012-01-01

    Purpose: To implement the “plan-do-check-act” (PDCA) cycle for the continual quality improvement of normal tissue contours used for radiation therapy treatment planning. Methods and Materials: The CT scans of patients treated for tumors of the brain, head and neck, thorax, pancreas and prostate were selected for this study. For each scan, a radiation oncologist and a diagnostic radiologist, outlined the normal tissues (“gold” contours) using Radiation Therapy Oncology Group (RTOG) guidelines. A total of 30 organs were delineated. Independently, 5 board-certified dosimetrists and 1 trainee then outlined the same organs. Metrics used to compare the agreement between the dosimetrists' contours and the gold contours included the Dice Similarity Coefficient (DSC), and a penalty function using distance to agreement. Based on these scores, dosimetrists were re-trained on those organs in which they did not receive a passing score, and they were subsequently re-tested. Results: Passing scores were achieved on 19 of 30 organs evaluated. These scores were correlated to organ volume. For organ volumes <8 cc, the average DSC was 0.61 vs organ volumes ≥8 cc, for which the average DSC was 0.91 (P=.005). Normal tissues that had the lowest scores included the lenses, optic nerves, chiasm, cochlea, and esophagus. Of the 11 organs that were considered for re-testing, 10 showed improvement in the average score, and statistically significant improvement was noted in more than half of these organs after education and re-assessment. Conclusions: The results of this study indicate the feasibility of applying the PDCA cycle to assess competence in the delineation of individual organs, and to identify areas for improvement. With testing, guidance, and re-evaluation, contouring consistency can be obtained across multiple dosimetrists. Our expectation is that continual quality improvement using the PDCA approach will ensure more accurate treatments and dose assessment in

  3. Oscillations of serum and tissue lipids in rats X-irradiated at different times of day

    International Nuclear Information System (INIS)

    Ahlers, I.; Ahlersova, E.; Toropila, M.; Smajda, B.; Praslicka, M.

    1983-01-01

    Young male Wistar rats (mean body mass 200 g) adapted to a 12:12 h light:dark regimen (7 a.m. to 7 p.m., 7 p.m. to 7 a.m.) were X-irradiated at 3-h intervals during one day with doses of 2.39 or 14.25 Gy and were killed 48 or 24 h afterwards. Nonesterified fatty acids were determined in their serum and white and brown adipose tissue, and triacylglycerols, phospholipids and total cholesterol in their serum and liver. The reaction of serum and tissue lipids during the day varied after both non-lethal and lethal irradiation. After non-lethal exposure, most of the curves, as regards their course, the presence of rhythm and their oscillation properties, concurred with the lipid indicator curves in the control series and indicated that the organism's response is dependent on the time of day. Circadian variation of serum and adipose tissue nonesterified fatty acid levels, the liver triacylglycerol concentration and the adrenal cholesterol concentration in lethally irradiated animals showed no significant dependence on the time of application of the stimulus. An analysis of circadian variation of the effectiveness of a stimulus facilitates understanding of the organism's reactivity better than a single examination in the morning. (author)

  4. Relationship between X-ray irradiation and chromosomal damage in bone marrow tissue of mice

    International Nuclear Information System (INIS)

    Chaubey, R.C.; George, K.P.; Sundaram, K.

    1976-01-01

    X-ray induced chromosomal damage in bone-marrow tissue of male mice was studied using micronucleus technique. Dose response relationship was evaluated. Male Swiss mice received whole body x-ray irradiation at different doses from 25-1000 rads. Animals were sacrificed at the end of 24 hours, bone-marrow smears were made and stained in May-Grunwald-Giemsa. The preparatians were scored for the following types of aberrations: micronuclei in young erythocytes-polychromatic cells and in the mature erythrocytes-normechromatic cells. A dose dependent increase in the frequency of micronuclei in polychromatic cells up to a dose of 100 rads was observed. In addition the effect of post-irradiation duration on the frequency of micronuclei in polychromatic and normochromatic cells were studied. Male Swiss mice were exposed to 200 rads x-rays and were then sacrificed at different time intervals after irradiation and bone-marrow preparations were made and scored. Maximum polychromatic cells with micronuclei were observed in 24 hours post-irradiated animals, thereafter a decrease in the frequency of polychromatic cells with micronuclei was observed in 40 hours post irradiated animals. (author

  5. Prodrugs designed to discriminate pathological (tumour) and physiological (normal tissue) hypoxia

    International Nuclear Information System (INIS)

    Wilson, W.R.; Patterson, A.V.

    2003-01-01

    There is now abundant evidence that hypoxic contributes to treatment failure in radiation therapy. As a target for therapeutic intervention, hypoxia is especially attractive because it is a common feature of most human tumours and therefore a potential 'pan target' across many tumour types. However, attempts to exploit hypoxia face the problem that oxygen concentrations in some normal tissues are also heterogeneous and that O 2 distributions in tumours and normal tissues overlap. Simply adjusting the K value (O 2 concentration for 50% inhibition of activation) does not provide a satisfactory solution. Bioreductive drugs like tirapazamine with high K values are activated significantly in several normal tissues, while nitro compounds and quinones with low K values spare the hypoxic tumour cells at 'intermediate' O 2 tensions (1-10 mM O 2 ) which are considered to be major contributors to tumour radioresistance. A potential strategy for overcoming this dilemma is to design prodrugs that are activated only at very low K values, but give relatively stable cytotoxic metabolites capable of diffusing to cells at higher O 2 concentrations. This approach redefines the therapeutic target as cells adjacent to zones of pathological hypoxia ( 2 ), providing discrimination from physiological hypoxia in normal tissues. Detecting bioreductive prodrugs capable of providing bystander killing of this kind is not straightforward. We have adapted a multicellular layer (MCL) co-culture model for quantifying bystander effects in GDEPT (Wilson et al., Cancer Res., 62: 1425-1432, 2002), and have used this to measure bystander effects of hypoxia-activated prodrugs. This model uses differences in metabolic activation of bioreductive drugs between A459 cell lines with low and high cytochrome P450 reductase activity, rather than O 2 gradients, to effect localised prodrug activation. It shows that TPZ and the nitroimidazole RSU-1069 have little or no bystander effect, but that dinitrobenzamide

  6. Increased CD147 and MMP-9 expression in the normal rat brain after gamma irradiation

    International Nuclear Information System (INIS)

    Li Hong; Wei Ming; Li Shenghui; Zhou Ziwei; Xu Desheng

    2013-01-01

    Radiation-induced vascular injury is a major complication of Gamma knife surgery (GKS). Previous studies have shown that CD147 and MMP-9 are closely associated with vascular remodeling and pathological angiogenesis. Thus, we analysed changes in CD147 and MMP-9 expression in the cerebral cortex to investigate the correlation between CD147 and MMP-9 in the rat following GKS. Adult male Wistar rats were subjected to GKS at a maximum dose of 75 Gy and then euthanized 1 to 12 weeks later. Using immunohistochemistry and western blot analysis, we found that CD147 and MMP-9 expression were markedly upregulated in the target area 8-12 weeks after GKS when compared with the control group. Immunofluorescent double staining demonstrated that CD147 signals colocalized with CD31, GFAP and MMP-9-positive cells. Importantly, CD147 levels correlated with increased MMP-9 expression in irradiated brain tissue. For the first time, these data demonstrate a potential relationship between CD147 and MMP-9 following GKS. In addition, our study also suggests that CD147 and MMP-9 may play a role in vascular injury after GKS. (author)

  7. A magnetic resonance imaging study on changes in rat mandibular bone marrow and pulp tissue after high-dose irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Wan; Lee, Byung Do [Dept. of Oral and Maxillofacial Radiology and Wonkwang Dental Research Institute, College of Dentistry, Wonkwang University, Iksan (Korea, Republic of); Lee, Kang Kyoo [Dept. of Radiation Oncology, School of Medicine, Wonkwang University, Iksan (Korea, Republic of); Koh, Kwang Joon [Dept. of Oral and Maxillofacial Radiology, School of Dentistry and Institute of Oral Bioscience, Chonbuk National University, Jeonju (Korea, Republic of)

    2014-03-15

    This study was designed to evaluate whether magnetic resonance imaging (MRI) is appropriate for detecting early changes in the mandibular bone marrow and pulp tissue of rats after high-dose irradiation. The right mandibles of Sprague-Dawley rats were irradiated with 10 Gy (Group 1, n=5) and 20 Gy (Group 2, n=5). Five non-irradiated animals were used as controls. The MR images of rat mandibles were obtained before irradiation and once a week until week 4 after irradiation. From the MR images, the signal intensity (SI) of the mandibular bone marrow and pulp tissue of the incisor was interpreted. The MR images were compared with the histopathologic findings. The SI of the mandibular bone marrow had decreased on T2-weighted MR images. There was little difference between Groups 1 and 2. The SI of the irradiated groups appeared to be lower than that of the control group. The histopathologic findings showed that the trabecular bone in the irradiated group had increased. The SI of the irradiated pulp tissue had decreased on T2-weighted MR images. However, the SI of the MR images in Group 2 was high in the atrophic pulp of the incisor apex at week 2 after irradiation. These patterns seen on MRI in rat bone marrow and pulp tissue were consistent with histopathologic findings. They may be useful to assess radiogenic sclerotic changes in rat mandibular bone marrow.

  8. Incorporation of tritiated thymidine and uridine in normal and endopolyploid nuclei of differentiated tissue

    International Nuclear Information System (INIS)

    Bansal, Y.K.; Sen, Sumitra

    1987-01-01

    Rate of replication and transcription between normal and giant endopolyploid nuclei of differentiated tissue of Hordeum vulgare L. (2n=14) roots and Phlox drummondii Hook. (2n=14) and Zea mays L. (2n=20) endosperms were studied by labelling experiments with tritiated thymidine and uridine. The incorporation of thymidine and uridine was identical in both diploid and giant endopolyploid nuclei of the roots of H. vulgare. The endosperm cells of P. drummondii and Z. mays, however, exhibit markedly different labelling pattern in normal (i.e. triploid) and endopolyploid nuclei where both replication and transcription were rather high. The nutritive function of the endosperm is probably responsible for this high degree of activity. (author). 14 refs., 10 figs., 3 tables

  9. Relaxation time of normal breast tissues. Changes with age and variations during the menstrual cycle

    International Nuclear Information System (INIS)

    Dean, K.I.; Majurin, M.L.; Komu, M.

    1994-01-01

    The influence of age on the relaxation times of normal breast parenchyma and its surrounding fatty tissue were evaluated, and the variations during a normal menstrual cycle were analyzed using an ultra low field 0.02 T imager. Thirty-nine healthy volunteers aged 21 to 59 years were examined to determine T1 and T2 relaxation times, and 8 of these volunteers were studied once weekly during one menstrual cycle. The only significant trend was an increase in the T2 of breast parenchyma with increasing age. During the menstrual cycle there was a slight but insignificant (p=0.10) increase in T1 of the breast parenchyma values during the latter half of the menstrual cycle, and a corresponding increase in T2 values between the 2nd and 3rd weeks of the menstrual cycle, which was significant. (orig.)

  10. Relaxation time of normal breast tissues. Changes with age and variations during the menstrual cycle

    Energy Technology Data Exchange (ETDEWEB)

    Dean, K.I. (University Central Hospital, Turku (Finland). Dept. of Diagnostic Radiology); Majurin, M.L. (University Central Hospital, Turku (Finland). Dept. of Diagnostic Radiology); Komu, M. (University Central Hospital, Turku (Finland). Dept. of Diagnostic Radiology)

    1994-05-01

    The influence of age on the relaxation times of normal breast parenchyma and its surrounding fatty tissue were evaluated, and the variations during a normal menstrual cycle were analyzed using an ultra low field 0.02 T imager. Thirty-nine healthy volunteers aged 21 to 59 years were examined to determine T1 and T2 relaxation times, and 8 of these volunteers were studied once weekly during one menstrual cycle. The only significant trend was an increase in the T2 of breast parenchyma with increasing age. During the menstrual cycle there was a slight but insignificant (p=0.10) increase in T1 of the breast parenchyma values during the latter half of the menstrual cycle, and a corresponding increase in T2 values between the 2nd and 3rd weeks of the menstrual cycle, which was significant. (orig.).

  11. The measurement of intrinsic cellular radiosensitivity in human tumours and normal tissues

    International Nuclear Information System (INIS)

    Lawton, P.A.

    1995-01-01

    Human tumour and normal cell radiosensitivity are thought to be important factors determining the response of tumour and normal tissues to radiotherapy, respectively. Clonogenic assays are the standard method for measuring radiosensitivity but they are of limited applicability for clinical use with fresh human tumours. The main aim of this work was to evaluate the Adhesive Tumour Cell Culture System (ATCCS), as a method for measuring the radiosensitivity of human tumours. A soft agar clonogenic assay, the modified Courtenay-Mills assay, was used as a standard to compare with the ATCCS. The demonstration that fibroblast contamination could occur with both assay methods led to the investigation of a new technique for removing unwanted fibroblasts from tumour cell suspensions and to the use of a multiwell assay for measuring fibroblast radiosensitivity. (author)

  12. The measurement of intrinsic cellular radiosensitivity in human tumours and normal tissues

    Energy Technology Data Exchange (ETDEWEB)

    Lawton, P.A.

    1995-12-31

    Human tumour and normal cell radiosensitivity are thought to be important factors determining the response of tumour and normal tissues to radiotherapy, respectively. Clonogenic assays are the standard method for measuring radiosensitivity but they are of limited applicability for clinical use with fresh human tumours. The main aim of this work was to evaluate the Adhesive Tumour Cell Culture System (ATCCS), as a method for measuring the radiosensitivity of human tumours. A soft agar clonogenic assay, the modified Courtenay-Mills assay, was used as a standard to compare with the ATCCS. The demonstration that fibroblast contamination could occur with both assay methods led to the investigation of a new technique for removing unwanted fibroblasts from tumour cell suspensions and to the use of a multiwell assay for measuring fibroblast radiosensitivity. (author).

  13. Comparison of radiosensitivity between tumor and normal tissue in terms of cell population kinetics

    International Nuclear Information System (INIS)

    Sugahara, Tsutomu; Utsumi, Hiroshi

    1975-01-01

    Puck and Marcus in 1956 established the in vitro colony formation of mammalian cells and demonstrated a dose-survival curve of mammalian cells well fitted to the target theory. Since then almost all of the work on the radiosensitivity of malignant and normal cells has been based on the reproductive integrity of cells. However, in the author's laboratory, a recent work was done on the effect of ionizing radiation on the differentiative trait, using clonal cell cultures developed by Coon (1966) in chick embryonic cartilage cells. This work demonstrated clearly that the differentiative trait is more radiosensitive than is reproduction. Based on this finding a new compartment model is proposed for a cell renewal system which demonstrates the difference between normal and malignant tissue. (author)

  14. Normal tissue adverse side effects in radiotherapy cancer patients and applicability of predictive radiosensitivity tests for new radiation treatment decision

    International Nuclear Information System (INIS)

    Di Giorgio, Marina; Vallerga, Maria B.; Radl, Analia; Sardi, Mabel

    2008-01-01

    Full text: Around 5 % -7 % of cancer patients develop adverse side effects, which include acute effects, late effects and cancer induction to radiation therapy in normal tissues in the treatment field. Such effects are of particular interest as the cancer patient population that reaches prolonged survival has increased with the improvements in cancer therapy and health care. These adverse reactions are mainly influenced by deficiencies in DNA repair pathways. However, tissue response to IR could be modified by several treatment- and patient- related factors. Numerous studies have been carried out to evaluate the correlation between clinical and cellular radiosensitivity, by in vitro tests. Previous own studies, characterizing DNA repair capacity in peripheral lymphocytes of cancer patients through cytokinesis blocked micronucleus test and alkaline single-cell microgel electrophoresis (comet), indicated that such assays correlated with the clinical radiation signs of radiosensitivity and showed the predictive potential of both techniques in the identification of radiosensitivity subgroups. In this paper, retrospective studies are conducted in 10 representative cases, which had developed acute or late toxicity in previous treatments and at present require new radiation treatments due to secondary malignancies or recurrence. Samples were in vitro irradiated with 2 Gy. MN data were analyzed comparing expected MN frequencies with values observed after in vitro irradiation. DNA repair capacity was evaluated through comet assay for initial damage and after specific times of repair (0-120 minutes). Captured images were analyzed by CASP image analysis software. Repair capacity was quantified by the Olive tail moment. Weibull alpha parameter was applied to describe DNA damage at the different evaluated repair times after in vitro irradiation and fitted by a mono-exponential model to describe the kinetic profile. In every evaluated patient a correlation between mean half

  15. Normal tissue adverse side effects in radiotherapy cancer patients and applicability of predictive radiosensitivity tests for new radiation treatment decision

    International Nuclear Information System (INIS)

    Di Giorgio, M.; Vallerga, M.B.; Radl, A.; Sardi, M.

    2011-01-01

    Around 5%-7% of cancer patients develop adverse side effects, which include acute effects, late effects and cancer induction to radiation therapy in normal tissues in the treatment field. Such effects are of particular interest as the cancer patient population that reaches prolonged survival has increased with the improvements in cancer therapy and health care. These adverse reactions are mainly influenced by deficiencies in DNA repair pathways. However, tissue response to IR could be modified by several treatment- and patient- related factors. Numerous studies have been carried out to evaluate the correlation between clinical and cellular radiosensitivity, by in vitro tests. Previous own studies, characterizing DNA repair capacity in peripheral lymphocytes of cancer patients through cytokinesis blocked micronucleus test and alkaline single-cell microgel electrophoresis (comet), indicated that such assays correlated with the clinical radiation signs of radiosensitivity and showed the predictive potential of both techniques in the identification of radiosensitivity subgroups. In this paper, retrospective studies are conducted in 10 representative cases, which had developed acute or late toxicity in previous treatments and at present require new radiation treatments due to secondary malignancies or recurrence. Samples were in vitro irradiated with 2 Gy. MN data were analyzed comparing expected MN frequencies with values observed after in vitro irradiation. DNA repair capacity was evaluated through comet assay for initial damage and after specific times of repair (0-120 minutes). Captured images were analyzed by CASP image analysis software. Repair capacity was quantified by the Olive tail moment. Weibull alpha parameter was applied to describe DNA damage at the different evaluated repair times after in vitro irradiation and fitted by a mono-exponential model to describe the kinetic profile. In every evaluated patient a correlation between mean half-time (T1/2) and

  16. Normal liver tissue sparing by intensity-modulated proton stereotactic body radiotherapy for solitary liver tumours

    International Nuclear Information System (INIS)

    Petersen, Joergen B. B.; Hansen, Anders T.; Lassen, Yasmin; Grau, Cai; Hoeyer, Morten; Muren, Ludvig P.

    2011-01-01

    Background. Stereotactic body radiotherapy (SBRT) is often the preferred treatment for the advanced liver tumours which owing to tumour distribution, size and multi-focality are out of range of surgical resection or radiofrequency ablation. However, only a minority of patients with liver tumours may be candidates for conventional SBRT because of the limited radiation tolerance of normal liver, intestine and other normal tissues. Due to the favourable depth-dose characteristics of protons, intensity-modulated proton therapy (IMPT) may be a superior alternative to photon-based SBRT. The purpose of this treatment planning study was therefore to investigate the potential sparing of normal liver by IMPT compared to photon-based intensity-modulated radiotherapy (IMRT) for solitary liver tumours. Material and methods. Ten patients with solitary liver metastasis treated at our institution with multi-field SBRT were retrospectively re-planned with IMRT and proton pencil beam scanning techniques. For the proton plans, two to three coplanar fields were used in contrast to five to six coplanar and non-coplanar photon fields. The same planning objectives were used for both techniques. A risk adapted dose prescription to the PTV surface of 12.5-16.75 Gy x 3 was used. Results. The spared liver volume for IMPT was higher compared to IMRT in all 10 patients. At the highest prescription dose level, the median liver volume receiving less than 15 Gy was 1411 cm 3 for IMPT and 955 cm 3 for IMRT (p D 15 Gy > 700 cm 3 constraint. For the D mean = 15 Gy constraint, nine of 10 cases could be treated at the highest dose level using IMPT whereas with IMRT, only two cases met this constraint at the highest dose level and six at the lowest dose level. Conclusion. A considerable sparing of normal liver tissue can be obtained using proton-based SBRT for solitary liver tumours

  17. Energetic heavy ions accelerate differentiation in the descendants of irradiated normal human diploid fibroblasts

    International Nuclear Information System (INIS)

    Hamada, Nobuyuki; Hara, Takamitsu; Funayama, Tomoo; Sakashita, Tetsuya; Kobayashi, Yasuhiko

    2008-01-01

    Ionizing radiation-induced genomic instability has been demonstrated in a variety of endpoints such as delayed reproductive death, chromosome instability and mutations, which occurs in the progeny of survivors many generations after the initial insult. Dependence of these effects on the linear energy transfer (LET) of the radiation is incompletely characterized; however, our previous work has shown that delayed reductions in clonogenicity can be most pronounced at LET of 108 keV/μm. To gain insight into potential cellular mechanisms involved in LET-dependent delayed loss of clonogenicity, we investigated morphological changes in colonies arising from normal human diploid fibroblasts exposed to γ-rays or energetic carbon ions (108 keV/μm). Exposure of confluent cultures to carbon ions was 4-fold more effective at inactivating cellular clonogenic potential and produced more abortive colonies containing reduced number of cells per colony than γ-rays. Second, colonies were assessed for clonal morphotypic heterogeneity. The yield of differentiated cells was elevated in a dose- and LET-dependent fashion in clonogenic colonies, whereas differentiated cells predominated to a comparable extent irrespective of radiation type or dose in abortive colonies. The incidence of giant or multinucleated cells was also increased but much less frequent than that of differentiated cells. Collectively, our results indicate that carbon ions facilitate differentiation more effectively than γ-rays as a major response in the progeny of irradiated fibroblasts. Accelerated differentiation may account, at least in part, for dose- and LET-dependent delayed loss of clonogenicity in normal human diploid cells, and could be a defensive mechanism that minimizes further expansion of aberrant cells

  18. Characteristics and function of bone marrow stromal adherent cells in normal and irradiated mice and guinea pigs

    Energy Technology Data Exchange (ETDEWEB)

    Changyu, Zheng; Ji, Liu; Xiaoying, Bi

    1986-04-01

    It has been shown from cytochemical and other characteristic studies of bone marrow stromal cells in CFU-F that there are seven types of stromal cells in the stromal adherent cell layer of normal and irradiated C/sub 57/ mice whereas there are only six types in guinea pigs. On the other hand, a radioresistant cell subtype appears in adherent layer after irradiation of both C/sub 57/ mice and guinea pig since the supernatant of cultured CFU-F of the normal and irradiated C/sub 57/ mice can stimulate production of CFU-Gm. It is justifiable that the bone marrow stromal adherent cells of the C/sub 57/ mice could produce CSF.

  19. Metabolism of neutral lipids in nuclei and chromatin of thymocytes from normal and γ-irradiated rats

    International Nuclear Information System (INIS)

    Kulagina, T.P.; Shuruta, S.A.; Kolomijtseva, I.K.

    1993-01-01

    The levels ans specific radioactivities of cholesterol and free fatty acids in nuclei and chromatin of thymocytes from normal and γ-irradiated (10 Gy) rats have been studied. The radioactivity of the total lipid fraction of γ-irradiated cells was decreased significantly in the absence of inhibition of [2- 14 C]acetete incorporation into the total proteil and lipid reactions and the [ 3 H]uracyl incorporation into the acid-insoluble RNA. The concentration of free fatty acids in the nuclei increased significantly after irradiation. The specific radioactivity of cholesterol in chromatin was higher than in the nuclei. The differences in specific radioactivities of free fatty acids were less pronounced. After irradiation the ratio of specific radioactivities of free fatty acids in chromatin to that in the nucleai showed a tendency to increase

  20. [Morphology of basement membrane and associated matrix proteins in normal and pathological tissues].

    Science.gov (United States)

    Nerlich, A

    1995-01-01

    Basement membranes (BM) are specialized structures of the extracellular matrix. Their composition is of particular importance for the maintenance of normal morphological and functional properties of a multitude of organs and tissue systems and it is thus required for regular homeostasis of body function. Generally, they possess three main functions, i.e. participation in the maintenance of tissue structure, control of fluid and substrate exchange, and regulation of cell growth and differentiation. BMs are made up by various components which are in part specifically localized within the BM zone, or which represent ubiquitous matrix constituents with specific quantitative and/or qualitative differences in their localization. On the basis of a thorough immunohistochemical analysis of normal and diseased tissues, we provide here a concept of "functional morphology/pathomorphology" of the different BM components analyzed: 1.) The ubiquitous BM-constituent collagen IV primarily stabilizes the BM-zone and thus represents the "backbone" of the BM providing mechanical strength. Its loss leads to cystic tissue transformation as it is evidenced from the analysis of polycystic nephropathies. Thus, in other cystic tissue transformations a similar formal pathogenesis may be present. 2.) The specific localization of collagen VII as the main structural component of anchoring fibrils underlines the mechanical anchoring function of this collagenous protein. Defects in this protein lead to hereditary epidermolysis. The rapid re-occurrence of epidermal collagen VII during normal human wound healing indicates a quick reconstitution of the mechanical tensile strength of healing wounds. 3.) The BM-specific heparan sulfate proteoglycan (HSPG, Perlecan) with its highly negative anionic charge can be assumed to exert filter control. This assumption is corroborated by the localizatory findings of a preferential deposition of HSPG in endothelial and particularly in glomerular BM. Similarly

  1. Influence of water and salt solutions on UVB irradiation of normal skin and psoriasis

    International Nuclear Information System (INIS)

    Boer, J.; Schothorst, A.A.; Boom, B.; Suurmond, D.; Hermans, J.

    1982-01-01

    The influence of tap-water (TW) and salt solutions on the minimal erythema dose (MED) was investigated for normal human skin and uninvolved skin of psoriasis patients. MED (UVB) determinations on the forearm revealed that: (1) the MED definitely decreases whenever the arm is immersed in TW or NaCl solutions with a low concentration (4%) prior to UVB exposure, whereas almost saturated NaCl solution (26%), as well as locum Dead Sea water (LDSW), do not produce a change in the MED, and (2) the decrease in MED obtained by wetting the skin with TW was no longer present when the skin was allowed to dry for 20 min. A decrease in water uptake by skin (in vivo) and by callus (in vitro) was found as the salt concentration of the external solution increased. It is proposed that water taken up by the skin plays an important role in the sensitivity of the skin to UVB exposure. Bathing in TW or 4% NaCl prior to UVB exposure offered a slight to moderate improvement in psoriasis over UVB irradiation alone. Finally, it was shown that there is no obvious difference in clearance of the psoriatic skin between a bath in TW, 4% NaCl, or LDSW prior to UVB exposure. (orig.)

  2. Up-regulation of calreticulin in mouse liver tissues after long-term irradiation with low-dose-rate gamma rays.

    Science.gov (United States)

    Yi, Lan; Hu, Nan; Yin, Jie; Sun, Jing; Mu, Hongxiang; Dai, Keren; Ding, Dexin

    2017-01-01

    The biological effects of low-dose or low-dose-rate ionizing radiation on normal tissues has attracted attention. Based on previous research, we observed the morphology of liver tissues of C57BL/6J mice that received irradiation dose rates increased. Additionally, differential protein expression in liver tissues was analyzed using a proteomics approach. Compared with the matched group in the 2D gel analysis of the irradiated groups, 69 proteins had ≥ 1.5-fold changes in expression. Twenty-three proteins were selected based on ≥2.5-fold change in expression, and 22 of them were meaningful for bioinformatics and protein fingerprinting analysis. These molecules were relevant to cytoskeleton processes, cell metabolism, biological defense, mitochondrial damage, detoxification and tumorigenesis. The results from real-time PCR and western blot (WB) analyses showed that calreticulin (CRT) was up-regulated in the irradiated groups, which indicates that CRT may be relevant to stress reactions when mouse livers are exposed to low-dose irradiation and that low-dose-rate ionizing radiation may pose a cancer risk. The CRT protein can be a potential candidate for low-dose or low-dose-rate ionizing radiation early-warning biomarkers. However, the underlying mechanism requires further investigation.

  3. Differential action on cancer and normal tissue by adrenochrome monoaminoguanidine methanesulfonate and cytochrome C combined with radiotherapy

    International Nuclear Information System (INIS)

    Nakatsugawa, S.; Sugahara, T.

    1994-01-01

    The possibility that radioprotective effects on potent natural killer (NK) cells by adrenochrome monoaminoguanidine methanesulfonate (AMM) + cytochrome C during radiotherapy (RT) for lung cancer might result in the radiosensitization of human lung cancer cells in vivo is examined. Human lung cancer xenografts in the right hind legs of KSN mice (10 weeks old) were locally irradiated with 20 Gy of X ray. AMM (10 mg/kg/day) and/or cytochrome C (CCC) (5 mg/kg/day) were given intraperitoneally immediately before or after RT, followed by daily administration for 4 days. Natural killer activities of host splenocytes were also tested with the standard 51 Cr releasing assay with YAC-1 cells as target cells. In a clinical study, 65 patients with lung cancer were treated with more than 50 Gy of RT with or without combination with AMM + CCC, OK-432 or AMM + CCC + OK-432. Before and after RT, lymphocyte subsets in the peripheral blood were examined with dichromatic analysis using an Ortho Spectrum IIIFCM system and fluorescent MABs. In this study, the change in the absolute number of each subset was investigated. AMM + cytochrome C augumented NK activity in KSN nude mice, protected potent NK cells in patients with lung cancer against RT and sensitized the human lung cancer xenografts to RT. AMM + cytochrome C may have potential as a differential modulator of radiosensitivity of normal tissues and of tumors. 8 refs., 2 figs., 1 tab

  4. Effect of different BNCT protocols on DNA synthesis in precancerous and normal tissues in an experimental model of oral cancer

    International Nuclear Information System (INIS)

    Heber, Elisa M.; Aromando, Romina; Trivillin, Veronica A.; Itoiz, Maria E.; Kreimann, Erica L.; Schwint, Amanda E.; Nigg, David W.

    2006-01-01

    We previously reported the therapeutic success of different BNCT protocols in the treatment of oral cancer, employing the hamster cheek pouch model. The aim of the present study was to evaluate the effect of these BNCT protocols on DNA synthesis in precancerous and normal tissue in this model and assess the potential lag in the development of second primary tumors in precancerous tissue. The data are relevant to potential control of field cancerized tissue and tolerance of normal tissue. We evaluated DNA synthesis in precancerous and normal pouch tissue 1-30 days post-BNCT mediated by BPA, GB-10 or BPA + GB-10 employing incorporation of bromo-deoxyuridine as an end-point. The BNCT-induced potential lag in the development of second primary tumors in precancerous tissue was monitored. A drastic, statistically significant reduction in DNA synthesis occurred in pacancerous tissue as early as 1 day post-BNCT and was sustained at virtually all time points until 30 days post-BNCT for all protocols. The histological categories evaluated individually within precancerous tissue (dysplasia, hyperplasia and NUMF [no unusual microscopic features]) responded similarly. DNA synthesis in normal tissue treated with BNCT oscillated around the very low pre-treatment values. A BNCT-induced lag in the development of second primary tumors was observed. BNCT induced a drastic fall in DNA synthesis in precancerous tissue that would be associated to the observed lag in the development of second primary tumors. The minimum variations in DNA synthesis in BNCT-treated normal tissue would correlate with the absence of normal tissue radiotoxicity. The present data would contribute to optimize therapeutic efficacy in the treatment of field-cancerized areas. (author)

  5. Reduction of dose enhancement from backscattered radiation at tissue-metal interfaces irradiated with 6MeV electrons

    International Nuclear Information System (INIS)

    Steel, B.

    1996-01-01

    Due to Electron Back Scatter (EBS), electron irradiation of tissue having under lying lead shielding results in an increase in dose to the tissue on the entrance side of the lead. In these situations dose increases as high as 80% have been reported in the literature. Saunders (British Journal of Radiology, 47, 467-470) noted that dose enhancement is dependent on atomic number of the under lying material approximately as Z 0.5 , and it increases at lower incident electron energies. In our clinic we use 2mm of lead shielding to protect under lying normal tissue when 6MeV electrons are used to treat lips and ears. The object of this study was to find the thinnest combination of materials to reduce the total dose to an acceptable level, with the provisos that; the patient does not come into contact with the lead or other metals, the finished shield could comfortabley be placed between the patient's lip and teeth, and that the materials are sufficietly malleable to work into custom shields. Various combinations of dental wax and aluminium were trialed. That which proved to give the best compromise between reduction of EBS and total shielding thickness was, 1mm of aluminim on the beam side of the lead with 1mm of dental wax to completely enclose the shield. In practice the manufactured shields are approximately 6 mm thick, and are usually not uncomfortable for the patient. (author)

  6. Clinical evaluation of normal tissue toxicity induced by ionizing radiation in cases of laryngeal carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Ramos, Adriano de Paula; Marques, Gustavo Inacio de Gomes; Soares, Renata da Bastos Ascenco; Dourado, Juliana Castro Dourado [Pontificia Universidade Catolica de Goias (PUCGO), Goiania, GO (Brazil). Dept. of Medicine; Mendonca, Yuri de Abreu, E-mail: renata.soares@pucgoias.edu.br [Goias Association Against Cancer, Goiania, GO (Brazil). Lab. of Radiobiology and Oncogenetics

    2012-07-01

    Laryngeal cancer is the second most frequent head and neck cancer in the Brazilian male population. For treatment, radiotherapy combined with chemotherapy is now used in substitution for total laryngectomy, becoming the standard treatment for advanced larynx cancer cases, with the aim of organ preservation. However, this method needs assessment of the side effects caused to normal tissue and organ functionality after treatment and the relation of these clinical factors to the individual characteristics of patients. Thus, the clinical characteristics of 229 patients with laryngeal cancer treated with radiotherapy were evaluated by medical records analysis in relation to normal tissue radiosensibility. Significant relations between smoking (p = 0.018) and combined chemoradiotherapy assistance (p = 0.03) were identified with high frequency of treatment suspension cases. The application of combined chemoradiotherapy also resulted in a higher incidence of oral mucositis (p = 0.04), xerostomia (p = 0.001) and treatment side effects to GIT (p = 0.04). Advanced clinical staging was associated with worse prognosis (p = 0.002) and a higher occurrence of treatment failure (p < 0.001). Radiotherapy was also less effective depending on the primary tumor location (p = 0.001). (author)

  7. Role of plasminogen activator inhibitor type-1 in radiation-induced normal tissues injury

    International Nuclear Information System (INIS)

    Abderrahmani, R.

    2010-01-01

    Radiotherapy is an essential tool for cancer treatment, but there is a balance between benefits and risks related to the use of ionizing radiation: the objective is to deliver a maximum dose to the tumour to destroy or to sterilize it while protecting surrounding normal tissues. Radio-induced damages to normal tissues are therefore a limiting factor when increasing the dose delivered to the tumour. One of the objectives of this research thesis is to bring to the fore a relationship between the initiation of lesions and the development of late damages, more particularly in the intestine, and to identify the involved molecular actors and their inter-connectivity. After a first part presenting ionizing radiation, describing biological effects of ionizing radiation and their use in radiotherapy, presenting the intestine and the endothelium and discussing the intestine radio-sensitivity, discussing the radio-induced intestine damages and radiotherapy-induced complications, and presenting the plasminogen activator inhibitor (PAI-1) and its behaviour in presence of ionizing radiation, two articles are reproduced. The first one addresses the effect of a pharmacological inhibition and of genetic deficiency in PAI-1 on the evolution of radio-induced intestine lesions. The second one discusses the fact that radio-induced PAI-1-related death of endothelial cells determines the severity of early radio-induced intestine lesions

  8. Comparison of soft-tissue orbital morphometry in attractive and normal Italian subjects.

    Science.gov (United States)

    Sforza, Chiarella; Dolci, Claudia; Grandi, Gaia; Tartaglia, Gianluca M; Laino, Alberto; Ferrario, Virgilio F

    2015-01-01

    To identify esthetic characteristics of the orbital soft tissues of attractive Italian adult women and men. Three-dimensional computerized digitizers were used to collect the coordinates of facial landmarks in 199 healthy, normal subjects aged 18 to 30 years (71 women, 128 men; mean age, 22 years) and in 126 coetaneous attractive subjects (92 women, 34 men; mean age, 20 years) selected during beauty competitions. From the landmarks, six linear distances, two ratios, six angles, and two areas were calculated. Attractive subjects were compared with normal ones by computing z-scores. Intercanthal width was reduced while eye fissure lengths were increased in both genders. Orbital heights (os-or) were increased only in attractive women, with a significant gender-related difference. The inclinations of the eye fissure were increased in attractive subjects, while the inclinations of the orbit were reduced. For several of the analyzed measurements, similar patterns of z-scores were observed for attractive men and women (r  =  .883). Attractive women and men had several specific esthetic characteristics in their orbital soft tissues; esthetic reference values can be used to determine optimal goals in surgical treatment.

  9. Immunohistochemical Expression of FXR1 in Canine Normal Tissues and Melanomas.

    Science.gov (United States)

    Nordio, Laura; Marques, Andreia T; Lecchi, Cristina; Luciano, Alberto M; Stefanello, Damiano; Giudice, Chiara

    2018-04-01

    Fragile X mental retardation-related protein 1 (FXR1) is a cytoplasmic RNA-binding protein highly conserved among vertebrates. It has been studied for its role in muscle development, inflammation, and tumorigenesis, being related, for example, to metastasizing behavior in human and canine uveal melanoma. Anti-FXR1 antibodies have never been validated in the canine species. To investigate FXR1 expression in canine melanocytic tumors, the present study tested two commercially available polyclonal anti-human FXR1 antibodies, raised in goat and rabbit, respectively. The cross-reactivity of the anti-FXR1 antibodies was assessed by Western blot analysis, and the protein was localized by IHC in a set of normal canine tissues and in canine melanocytic tumors (10 uveal and 10 oral). Western blot results demonstrated that the antibody raised in rabbit specifically recognized the canine FXR1, while the antibody raised in goat did not cross-react with this canine protein. FXR1 protein was immunodetected using rabbit anti-FXR1 antibody, in canine normal tissues with different levels of intensity and distribution. It was also detected in 10/10 uveal and 9/10 oral melanocytic tumors. The present study validated for the first time the use of anti-FXR1 antibody in dogs and highlighted different FXR1 protein expression in canine melanocytic tumors, the significance of which is undergoing further investigations.

  10. Mammary stem cell and macrophage markers are enriched in normal tissue adjacent to inflammatory breast cancer.

    Science.gov (United States)

    Reddy, Jay P; Atkinson, Rachel L; Larson, Richard; Burks, Jared K; Smith, Daniel; Debeb, Bisrat G; Ruffell, Brian; Creighton, Chad J; Bambhroliya, Arvind; Reuben, James M; Van Laere, Steven J; Krishnamurthy, Savitri; Symmans, William F; Brewster, Abenaa M; Woodward, Wendy A

    2018-06-01

    We hypothesized that breast tissue not involved by tumor in inflammatory breast cancer (IBC) patients contains intrinsic differences, including increased mammary stem cells and macrophage infiltration, which may promote the IBC phenotype. Normal breast parenchyma ≥ 5 cm away from primary tumors was obtained from mastectomy specimens. This included an initial cohort of 8 IBC patients and 60 non-IBC patients followed by a validation cohort of 19 IBC patients and 25 non-IBC patients. Samples were immunostained for either CD44 + CD49f + CD133/2 + mammary stem cell markers or the CD68 macrophage marker and correlated with IBC status. Quantitation of positive cells was determined using inForm software from PerkinElmer. We also examined the association between IBC status and previously published tumorigenic stem cell and IBC tumor signatures in the validation cohort samples. 8 of 8 IBC samples expressed isolated CD44 + CD49f + CD133/2 + stem cell marked cells in the initial cohort as opposed to 0/60 non-IBC samples (p = 0.001). Similarly, the median number of CD44 + CD49f + CD133/2 + cells was significantly higher in the IBC validation cohort as opposed to the non-IBC validation cohort (25.7 vs. 14.2, p = 0.007). 7 of 8 IBC samples expressed CD68 + histologically confirmed macrophages in initial cohort as opposed to 12/48 non-IBC samples (p = 0.001). In the validation cohort, the median number of CD68 + cells in IBC was 3.7 versus 1.0 in the non-IBC cohort (p = 0.06). IBC normal tissue was positively associated with a tumorigenic stem cell signature (p = 0.02) and with a 79-gene IBC signature (p stem cell signature and IBC-specific tumor signature. Collectively, these data suggest that IBC normal tissue differs from non-IBC tissue. Whether these changes occur before the tumor develops or is induced by tumor warrants further investigation.

  11. Comparison of the effect between an active specific immunotherapy using the immune reaction of a low-dose irradiated tumor tissue and that using irradiated tumor cells

    International Nuclear Information System (INIS)

    Ogawa, Yasuhiro; Maeda, Tomoho; Yoshida, Shoji; Yamamoto, Yoichi; Morita, Masaru

    1983-01-01

    The effect of the active specific immunotherapy using the immune reaction of a low-dose irradiated tumor tissue was compared with that of irradiated (10,000 rads) tumor cells on the transplanted MM46 tumor of female C3H/He mice after radiotherapy. MM46 tumor cells were inoculated into the right hind paws of mice. On the 6th day, irradiation with a dose of 3,000 rads was performed. On the 14th day, tumor cells and concomitant mononuclear cells which were separated from the low-dose irradiated tumor tissue (2,000 rads on the 6th day) were injected into the left hind paws of one group of the tumor-bearing mice. On the same day, irradiated MM46 tumor cells were injected into the left hind paws of another group of the tumor-bearing mice. Effectiveness of these two methods of active specific immunotherapy against tumor was evaluated by the regression of tumor and survival rate of mice. The active specific immunotherapy using the immune reaction of a low-dose irradiated tumor tissue was far more effective than irradiated tumor cells on this tumor system involved. (author)

  12. Effect of irradiation on cell cycle, cell death and expression of its related proteins in normal human oral keratinocytes

    International Nuclear Information System (INIS)

    Kang, Mi Ae; Heo, Min Suk; Lee, Sam Sun; Oh, Sung Ook; Choi, Soon Chul; Park, Tae Won; Lee, Sul Mi; Jeon, In Seong

    2003-01-01

    To investigate the radiosensitivity of the normal human oral keratinocytes (NHOK), and the effect of irradiation on cell cycle and protein expression. To evaluate the radiosensitivity of NHOK, the number of colonies and cells were counted after irradiation and the SF2 (survival fraction as 2 Gy) value, and the cell survival curve fitted on a linear-quadratic model were obtained. LDH analysis was carried out to evaluate the necrosis of NHOK at 1, 2,3, and 4 days after 2, 10, and 20 Gy irradiation. Cell cycle arrest and the induction of apoptosis were analyzed using flow cytometry at 1, 2, 3, and 4 days after 2, 10, and 20 Gy irradiation. Finally, proteins related cell cycle arrest and apoptosis were analysed by Western blot. The number of survival cell was significantly decreased in a dose-dependent manner. The cell survival curve showed SF2, α, and β values to be 0.568, 0.209, and 0.020 respectively. At 20 Gy irradiated cells showed higher optical density than the control group. After irradiation, apoptosis was not observed but G2 arrest was observed in the NHOK cells. 1 day after 10 Gy irradiation, the expression of p53 remained unchanged, the p21 WAF1/Cip1 increased and the mdm2 decreased. The expression of bax, bcl-2, cyclin B1, and cyclin D remained unchanged. These results indicate that NHOK responds to irradiation by G2 arrest, which is possibly mediated by the expression of p21 WAF1/Cip1 , and that cell necrosis occurs by high dose irradiation.

  13. Changes of the lactate dehydrogenase in the tissue fraction with Walker carcinoma under irradiation

    International Nuclear Information System (INIS)

    Schultheis, W.

    1972-01-01

    The behaviour of LDH, GOT and GPT of one and the same tissue with and without irradiation treatment as a means of cancer diagnosis is presented. Parallel to this, the corresponding blood values are determined, and an agar-gel isoenzyme separation of the LDH is carried out. In the 11 day-old Walker carcinoma of the rat, total tumour LDH as well as total serum LDH are increased. The X-radiation does not affect the result. The M 4 isoenzyme is mainly found in the tumour tissue, to whose benefit the tumour sera also change. In tissue processing, LDH, GOT and GPT behave corresponding to their occurence in the cell compartments. The enzymes, however, appear to differ in their solution behaviour. X-radiation leeds to an early removal of these enzymes in the sense of an 'enzyme release'. (BSC/LH) [de

  14. Is NAA reduction in normal contralateral cerebral tissue in stroke patients dependent on underlying risk factors?

    Science.gov (United States)

    Walker, P M; Ben Salem, D; Giroud, M; Brunotte, F

    2006-05-01

    This retrospective study investigated the dependence of N-acetyl aspartate (NAA) ratios on risk factors for cerebral vasculopathy such as sex, age, hypertension, diabetes mellitus, carotid stenosis, and dyslipidaemia, which may have affected brain vessels and induced metabolic brain abnormalities prior to stroke. We hypothesise that in stroke patients metabolic alterations in the apparently normal contralateral brain are dependent on the presence or not of such risk factors. Fifty nine patients (31 male, 28 female: 58.8+/-16.1 years old) with cortical middle cerebral artery (MCA) territory infarction were included. Long echo time chemical shift imaging spectroscopy was carried out on a Siemens 1.5 T Magnetom Vision scanner using a multi-voxel PRESS technique. Metabolite ratios (NAA/choline, NAA/creatine, lactate/choline, etc) were studied using uni- and multivariate analyses with respect to common risk factors. The influence of age, stroke lesion size, and time since stroke was studied using a linear regression approach. Age, sex, and hypertension all appeared to individually influence metabolite ratios, although only hypertension was significant after multivariate analysis. In both basal ganglia and periventricular white matter regions in apparently normal contralateral brain, the NAA/choline ratio was significantly lower in hypertensive (1.37+/-0.16 and 1.50+/-0.19, respectively) than in normotensive patients (1.72+/-0.19 and 1.85+/-0.15, respectively). Regarding MCA infarction, contralateral tissue remote from the lesion behaves abnormally in the presence of hypertension, the NAA ratios in hypertensive patients being significantly lower. These data suggest that hypertension may compromise the use of contralateral tissue data as a reference for comparison with ischaemic tissue.

  15. Elastic moduli of normal and pathological human breast tissues: an inversion-technique-based investigation of 169 samples

    International Nuclear Information System (INIS)

    Samani, Abbas; Zubovits, Judit; Plewes, Donald

    2007-01-01

    Understanding and quantifying the mechanical properties of breast tissues has been a subject of interest for the past two decades. This has been motivated in part by interest in modelling soft tissue response for surgery planning and virtual-reality-based surgical training. Interpreting elastography images for diagnostic purposes also requires a sound understanding of normal and pathological tissue mechanical properties. Reliable data on tissue elastic properties are very limited and those which are available tend to be inconsistent, in part as a result of measurement methodology. We have developed specialized techniques to measure tissue elasticity of breast normal tissues and tumour specimens and applied them to 169 fresh ex vivo breast tissue samples including fat and fibroglandular tissue as well as a range of benign and malignant breast tumour types. Results show that, under small deformation conditions, the elastic modulus of normal breast fat and fibroglandular tissues are similar while fibroadenomas were approximately twice the stiffness. Fibrocystic disease and malignant tumours exhibited a 3-6-fold increased stiffness with high-grade invasive ductal carcinoma exhibiting up to a 13-fold increase in stiffness compared to fibrogalndular tissue. A statistical analysis showed that differences between the elastic modulus of the majority of those tissues were statistically significant. Implications for the specificity advantages of elastography are reviewed

  16. Elastic moduli of normal and pathological human breast tissues: an inversion-technique-based investigation of 169 samples

    Energy Technology Data Exchange (ETDEWEB)

    Samani, Abbas [Department of Medical Biophysics/Electrical and Computer Engineering, University of Western Ontario, Medical Sciences Building, London, Ontario, N6A 5C1 (Canada); Zubovits, Judit [Department of Anatomic Pathology, Sunnybrook Health Sciences Centre, 2075 Bayview Avenue, Toronto, Ontario, M4N 3M5 (Canada); Plewes, Donald [Department of Medical Biophysics, University of Toronto, 2075 Bayview Avenue, Toronto, Ontario, M4N 3M5 (Canada)

    2007-03-21

    Understanding and quantifying the mechanical properties of breast tissues has been a subject of interest for the past two decades. This has been motivated in part by interest in modelling soft tissue response for surgery planning and virtual-reality-based surgical training. Interpreting elastography images for diagnostic purposes also requires a sound understanding of normal and pathological tissue mechanical properties. Reliable data on tissue elastic properties are very limited and those which are available tend to be inconsistent, in part as a result of measurement methodology. We have developed specialized techniques to measure tissue elasticity of breast normal tissues and tumour specimens and applied them to 169 fresh ex vivo breast tissue samples including fat and fibroglandular tissue as well as a range of benign and malignant breast tumour types. Results show that, under small deformation conditions, the elastic modulus of normal breast fat and fibroglandular tissues are similar while fibroadenomas were approximately twice the stiffness. Fibrocystic disease and malignant tumours exhibited a 3-6-fold increased stiffness with high-grade invasive ductal carcinoma exhibiting up to a 13-fold increase in stiffness compared to fibrogalndular tissue. A statistical analysis showed that differences between the elastic modulus of the majority of those tissues were statistically significant. Implications for the specificity advantages of elastography are reviewed.

  17. Elastic moduli of normal and pathological human breast tissues: an inversion-technique-based investigation of 169 samples

    Science.gov (United States)

    Samani, Abbas; Zubovits, Judit; Plewes, Donald

    2007-03-01

    Understanding and quantifying the mechanical properties of breast tissues has been a subject of interest for the past two decades. This has been motivated in part by interest in modelling soft tissue response for surgery planning and virtual-reality-based surgical training. Interpreting elastography images for diagnostic purposes also requires a sound understanding of normal and pathological tissue mechanical properties. Reliable data on tissue elastic properties are very limited and those which are available tend to be inconsistent, in part as a result of measurement methodology. We have developed specialized techniques to measure tissue elasticity of breast normal tissues and tumour specimens and applied them to 169 fresh ex vivo breast tissue samples including fat and fibroglandular tissue as well as a range of benign and malignant breast tumour types. Results show that, under small deformation conditions, the elastic modulus of normal breast fat and fibroglandular tissues are similar while fibroadenomas were approximately twice the stiffness. Fibrocystic disease and malignant tumours exhibited a 3-6-fold increased stiffness with high-grade invasive ductal carcinoma exhibiting up to a 13-fold increase in stiffness compared to fibrogalndular tissue. A statistical analysis showed that differences between the elastic modulus of the majority of those tissues were statistically significant. Implications for the specificity advantages of elastography are reviewed.

  18. Utility of Normal Tissue-to-Tumor {alpha}/{beta} Ratio When Evaluating Isodoses of Isoeffective Radiation Therapy Treatment Plans

    Energy Technology Data Exchange (ETDEWEB)

    Gay, Hiram A., E-mail: hgay@radonc.wustl.edu [Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri (United States); Jin Jianyue [Department of Radiation Oncology, Henry Ford Hospital, Detroit, Michigan (United States); Chang, Albert J. [Department of Radiation Oncology, University of California, San Francisco, California (United States); Ten Haken, Randall K. [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States)

    2013-01-01

    Purpose: To achieve a better understanding of the effect of the number of fractions on normal tissue sparing for equivalent tumor control in radiation therapy plans by using equivalent biologically effective dose (BED) isoeffect calculations. Methods and Materials: The simple linear quadratic (LQ) model was assumed to be valid up to 10 Gy per fraction. Using the model, we formulated a well-known mathematical equality for the tumor prescription dose and probed and solved a second mathematical problem for normal tissue isoeffect. That is, for a given arbitrary relative isodose distribution (treatment plan in percentages), 2 isoeffective tumor treatment regimens (N fractions of the dose D and n fractions of the dose d) were denoted, which resulted in the same BED (corresponding to 100% prescription isodose). Given these situations, the LQ model was further exploited to mathematically establish a unique relative isodose level, z (%), for the same arbitrary treatment plan, where the BED to normal tissues was also isoeffective for both fractionation regimens. Results: For the previously stated problem, the relative isodose level z (%), where the BEDs to the normal tissue were also equal, was defined by the normal tissue {alpha}/{beta} ratio divided by the tumor {alpha}/{beta} times 100%. Fewer fractions offers a therapeutic advantage for those portions of the normal tissue located outside the isodose surface, z, whereas more fractions offer a therapeutic advantage for those portions of the normal tissue within the isodose surface, z. Conclusions: Relative isodose-based treatment plan evaluations may be useful for comparing isoeffective tumor regimens in terms of normal tissue effects. Regions of tissues that would benefit from hypofractionation or standard fractionation can be identified.

  19. A mast cell secretagogue, compound 48/80, prevents the accumulation of hyaluronan in lung tissue injured by ionizing irradiation

    International Nuclear Information System (INIS)

    Nilsson, K.; Bjermer, L.; Hellstroem, S.H.; Henriksson, R.; Haellgren, R.

    1990-01-01

    Irradiation with a single dose of 30 Grey on the basal regions of the lungs of Sprague-Dawley rats induced a peribronchial and alveolar inflammation. Infiltration of mast cells in the edematous alveolar interstitial tissue and also in the peribronchial tissue were characteristic features of the lesion. The appearance of mast cells was already seen 4 wk after irradiation and by weeks 6 to 8 there was a heavy infiltration. The staining properties suggested that they were connective tissue-type mast cells. The infiltration of mast cells was paralleled by an accumulation of hyaluronan (hyaluronic acid) in the alveolar interstitial tissue 6 and 8 wk after irradiation. The recovery of hyaluronan (HA) during bronchoalveolar lavage (BAL) of the lungs also increased at this time. Treatment with a mast cell secretagogue, compound 48/80, induced a distinct reduction of granulated mast cells in the alveolar tissue. Regular treatment with compound 48/80 from the time of irradiation considerably reduced the HA recovery during BAL and the HA accumulation in the interstitial tissue but did not affect the interstitial infiltration of mononuclear cells and polymorphonuclear leukocytes. By contrast, an accumulation of HA in the alveolar interstitial space was induced when compound 48/80 was given not until mast cell infiltration of the lung had started. The effects of compound 48/80 indicate that the connective tissue response after lung irradiation is dependent on whether or not mast cell degranulation is induced before or after the mast cell infiltration of the alveolar tissue

  20. Compton scattering spectrum as a source of information of normal and neoplastic breast tissues' composition

    Energy Technology Data Exchange (ETDEWEB)

    Antoniassi, M.; Conceicao, A.L.C. [Departamento de Fisica-Faculdade de Filosofia Ciencias e Letras de Ribeirao Preto, Universidade de Sao Paulo, Ribeirao Preto, 14040-901 Sao Paulo (Brazil); Poletti, M.E., E-mail: poletti@ffclrp.usp.br [Departamento de Fisica-Faculdade de Filosofia Ciencias e Letras de Ribeirao Preto, Universidade de Sao Paulo, Ribeirao Preto, 14040-901 Sao Paulo (Brazil)

    2012-07-15

    In this work we measured X-ray scatter spectra from normal and neoplastic breast tissues using photon energy of 17.44 keV and a scattering angle of 90 Degree-Sign , in order to study the shape (FWHM) of the Compton peaks. The obtained results for FWHM were discussed in terms of composition and histological characteristics of each tissue type. The statistical analysis shows that the distribution of FWHM of normal adipose breast tissue clearly differs from all other investigated tissues. Comparison between experimental values of FWHM and effective atomic number revealed a strong correlation between them, showing that the FWHM values can be used to provide information about elemental composition of the tissues. - Highlights: Black-Right-Pointing-Pointer X-ray scatter spectra from normal and neoplastic breast tissues were measured. Black-Right-Pointing-Pointer Shape (FWHM) of Compton peak was related with elemental composition and characteristics of each tissue type. Black-Right-Pointing-Pointer A statistical hypothesis test showed clear differences between normal and neoplastic breast tissues. Black-Right-Pointing-Pointer There is a strong correlation between experimental values of FWHM and effective atomic number. Black-Right-Pointing-Pointer Shape (FWHM) of Compton peak can be used to provide information about elemental composition of the tissues.

  1. A large-scale study of the ultrawideband microwave dielectric properties of normal breast tissue obtained from reduction surgeries.

    Science.gov (United States)

    Lazebnik, Mariya; McCartney, Leah; Popovic, Dijana; Watkins, Cynthia B; Lindstrom, Mary J; Harter, Josephine; Sewall, Sarah; Magliocco, Anthony; Booske, John H; Okoniewski, Michal; Hagness, Susan C

    2007-05-21

    The efficacy of emerging microwave breast cancer detection and treatment techniques will depend, in part, on the dielectric properties of normal breast tissue. However, knowledge of these properties at microwave frequencies has been limited due to gaps and discrepancies in previously reported small-scale studies. To address these issues, we experimentally characterized the wideband microwave-frequency dielectric properties of a large number of normal breast tissue samples obtained from breast reduction surgeries at the University of Wisconsin and University of Calgary hospitals. The dielectric spectroscopy measurements were conducted from 0.5 to 20 GHz using a precision open-ended coaxial probe. The tissue composition within the probe's sensing region was quantified in terms of percentages of adipose, fibroconnective and glandular tissues. We fit a one-pole Cole-Cole model to the complex permittivity data set obtained for each sample and determined median Cole-Cole parameters for three groups of normal breast tissues, categorized by adipose tissue content (0-30%, 31-84% and 85-100%). Our analysis of the dielectric properties data for 354 tissue samples reveals that there is a large variation in the dielectric properties of normal breast tissue due to substantial tissue heterogeneity. We observed no statistically significant difference between the within-patient and between-patient variability in the dielectric properties.

  2. A large-scale study of the ultrawideband microwave dielectric properties of normal breast tissue obtained from reduction surgeries

    International Nuclear Information System (INIS)

    Lazebnik, Mariya; McCartney, Leah; Popovic, Dijana; Watkins, Cynthia B; Lindstrom, Mary J; Harter, Josephine; Sewall, Sarah; Magliocco, Anthony; Booske, John H; Okoniewski, Michal; Hagness, Susan C

    2007-01-01

    The efficacy of emerging microwave breast cancer detection and treatment techniques will depend, in part, on the dielectric properties of normal breast tissue. However, knowledge of these properties at microwave frequencies has been limited due to gaps and discrepancies in previously reported small-scale studies. To address these issues, we experimentally characterized the wideband microwave-frequency dielectric properties of a large number of normal breast tissue samples obtained from breast reduction surgeries at University of Wisconsin and University of Calgary hospitals. The dielectric spectroscopy measurements were conducted from 0.5 to 20 GHz using a precision open-ended coaxial probe. The tissue composition within the probe's sensing region was quantified in terms of percentages of adipose, fibroconnective and glandular tissues. We fit a one-pole Cole-Cole model to the complex permittivity data set obtained for each sample and determined median Cole-Cole parameters for three groups of normal breast tissues, categorized by adipose tissue content (0-30%, 31-84% and 85-100%). Our analysis of the dielectric properties data for 354 tissue samples reveals that there is a large variation in the dielectric properties of normal breast tissue due to substantial tissue heterogeneity. We observed no statistically significant difference between the within-patient and between-patient variability in the dielectric properties

  3. Metabolic Profiling of Somatic Tissues from Monochamus alternatus (Coleoptera: Cerambycidae Reveals Effects of Irradiation on Metabolism

    Directory of Open Access Journals (Sweden)

    Liangjian Qu

    2014-06-01

    Full Text Available A high-level of sexual sterility is of importance for the sterile insect technique (SIT. However, the use of high-dose-intensity gamma radiation to induce sterility has negative impacts not only on reproductive cells but also on somatic cells. In this study, we investigated the metabolite differences in somatic tissues between non-irradiated, 20-Gy-irradiated, and 40-Gy-irradiated male Monochamus alternatus, an important vector of the pathogenic nematode, Bursaphelenchus xylophilus, which kills Asian pines. The results showed that metabolite levels changed moderately in the 20-Gy samples but were markedly altered in the 40-Gy samples compared with the non-irradiated samples. Twenty-six and 53 metabolites were disturbed by 20-Gy and 40-Gy radiation, respectively. Thirty-six metabolites were found to be markedly altered in the 40-Gy samples but were not changed significantly in the 20-Gy samples. The comprehensive metabolomic disorders induced by 40-Gy radiation dysregulated six metabolic pathways involved in the life process. The findings presented in this manuscript will contribute to our knowledge of the characteristic metabolic changes associated with gamma-radiation-induced damage to somatic cells and will allow for better exploration of the SIT for the control of this target pest.

  4. Cell-surface glycoproteins of human sarcomas: differential expression in normal and malignant tissues and cultured cells

    International Nuclear Information System (INIS)

    Rettig, W.F.; Garin-Chesa, P.; Beresford, H.R.; Oettgen, H.F.; Melamed, M.R.; Old, L.J.

    1988-01-01

    Normal differentiation and malignant transformation of human cells are characterized by specific changes in surface antigen phenotype. In the present study, the authors have defined six cell-surface antigens of human sarcomas and normal mesenchymal cells, by using mixed hemadsorption assays and immunochemical methods for the analysis of cultured cells and immunohistochemical staining for the analysis of normal tissues and > 200 tumor specimens. Differential patterns of F19, F24, G171, G253, S5, and Thy-1 antigen expression were found to characterize (i) subsets of cultured sarcoma cell lines, (ii) cultured fibroblasts derived from various organs, (iii) normal resting and activated mesenchymal tissues, and (iv) sarcoma and nonmesenchymal tumor tissues. These results provide a basic surface antigenic map for cultured mesenchymal cells and mesenchymal tissues and permit the classification of human sarcomas according to their antigenic phenotypes

  5. Radiation-induced DNA damage in tumors and normal tissues. II. Influence of dose, residual DNA damage and physiological factors in oxygenated cells

    International Nuclear Information System (INIS)

    Zhang, H.; Wheeler, K.T.

    1994-01-01

    Detection and quantification of hypoxic cells in solid tumors is important for many experimental and clinical situations. Several laboratories, including ours, have suggested that assays which measure radiation-induced DNA strand breaks and DNA-protein crosslinks (DPCs) might be used to detect or quantify hypoxic cells in tumors and normal tissues. Recently, we demonstrated the feasibility of using an alkaline elution assay that measures strand breaks and DPCs to detect and/or quantify hypoxic cells in tissues. For this approach to be valid, DPCs must not be formed to any great extent in irradiated oxygenated cells, and the formation and repair of strand breaks and DPCs in oxygenated cells must not be modified appreciably by physiological factors (e.g., temperature, pH and nutrient depletion) that are often found in solid tumors. To address these issues, two sets of experiments were performed. In one set of experiments, oxygenated 9L cells in tissue culture, subcutaneous 9L tumors and rat cerebella were irradiated with doses of 15 or 50 Gy and allowed to repair until the residual strand break damage was low enough to detect DPCs. In another set of experiments, oxygenated exponentially growing or plateau-phase 9L cells in tissue culture were irradiated with a dose of 15 Gy at 37 or 20 degrees C, while the cells were maintained at a pH of either 6.6 or 7.3. DNA-protein crosslinks were formed in oxygenated cells about 100 times less efficiently than in hypoxic cells. In addition, temperature, pH, nutrient depletion and growth phase did not appreciably alter the formation and repair of strand breaks or the formation of DPCs in oxygenated 9L cells. These results support the use of this DNA damage assay for the detection and quantification of hypoxic cells in solid tumors. 27 refs., 5 tabs

  6. Towards the intrahour forecasting of direct normal irradiance using sky-imaging data.

    Science.gov (United States)

    Nou, Julien; Chauvin, Rémi; Eynard, Julien; Thil, Stéphane; Grieu, Stéphane

    2018-04-01

    Increasing power plant efficiency through improved operation is key in the development of Concentrating Solar Power (CSP) technologies. To this end, one of the most challenging topics remains accurately forecasting the solar resource at a short-term horizon. Indeed, in CSP plants, production is directly impacted by both the availability and variability of the solar resource and, more specifically, by Direct Normal Irradiance (DNI). The present paper deals with a new approach to the intrahour forecasting (the forecast horizon [Formula: see text] is up to [Formula: see text] ahead) of DNI, taking advantage of the fact that this quantity can be split into two terms, i.e. clear-sky DNI and the clear sky index. Clear-sky DNI is forecasted from DNI measurements, using an empirical model (Ineichen and Perez, 2002) combined with a persistence of atmospheric turbidity. Moreover, in the framework of the CSPIMP (Concentrating Solar Power plant efficiency IMProvement) research project, PROMES-CNRS has developed a sky imager able to provide High Dynamic Range (HDR) images. So, regarding the clear-sky index, it is forecasted from sky-imaging data, using an Adaptive Network-based Fuzzy Inference System (ANFIS). A hybrid algorithm that takes inspiration from the classification algorithm proposed by Ghonima et al. (2012) when clear-sky anisotropy is known and from the hybrid thresholding algorithm proposed by Li et al. (2011) in the opposite case has been developed to the detection of clouds. Performance is evaluated via a comparative study in which persistence models - either a persistence of DNI or a persistence of the clear-sky index - are included. Preliminary results highlight that the proposed approach has the potential to outperform these models (both persistence models achieve similar performance) in terms of forecasting accuracy: over the test data used, RMSE (the Root Mean Square Error) is reduced of about [Formula: see text], with [Formula: see text], and [Formula: see

  7. Semi-empirical models for the estimation of clear sky solar global and direct normal irradiances in the tropics

    International Nuclear Information System (INIS)

    Janjai, S.; Sricharoen, K.; Pattarapanitchai, S.

    2011-01-01

    Highlights: → New semi-empirical models for predicting clear sky irradiance were developed. → The proposed models compare favorably with other empirical models. → Performance of proposed models is comparable with that of widely used physical models. → The proposed models have advantage over the physical models in terms of simplicity. -- Abstract: This paper presents semi-empirical models for estimating global and direct normal solar irradiances under clear sky conditions in the tropics. The models are based on a one-year period of clear sky global and direct normal irradiances data collected at three solar radiation monitoring stations in Thailand: Chiang Mai (18.78 o N, 98.98 o E) located in the North of the country, Nakhon Pathom (13.82 o N, 100.04 o E) in the Centre and Songkhla (7.20 o N, 100.60 o E) in the South. The models describe global and direct normal irradiances as functions of the Angstrom turbidity coefficient, the Angstrom wavelength exponent, precipitable water and total column ozone. The data of Angstrom turbidity coefficient, wavelength exponent and precipitable water were obtained from AERONET sunphotometers, and column ozone was retrieved from the OMI/AURA satellite. Model validation was accomplished using data from these three stations for the data periods which were not included in the model formulation. The models were also validated against an independent data set collected at Ubon Ratchathani (15.25 o N, 104.87 o E) in the Northeast. The global and direct normal irradiances calculated from the models and those obtained from measurements are in good agreement, with the root mean square difference (RMSD) of 7.5% for both global and direct normal irradiances. The performance of the models was also compared with that of other models. The performance of the models compared favorably with that of empirical models. Additionally, the accuracy of irradiances predicted from the proposed model are comparable with that obtained from some

  8. Fractionation in normal tissues: the (α/β)eff concept can account for dose heterogeneity and volume effects.

    Science.gov (United States)

    Hoffmann, Aswin L; Nahum, Alan E

    2013-10-07

    The simple Linear-Quadratic (LQ)-based Withers iso-effect formula (WIF) is widely used in external-beam radiotherapy to derive a new tumour dose prescription such that there is normal-tissue (NT) iso-effect when changing the fraction size and/or number. However, as conventionally applied, the WIF is invalid unless the normal-tissue response is solely determined by the tumour dose. We propose a generalized WIF (gWIF) which retains the tumour prescription dose, but replaces the intrinsic fractionation sensitivity measure (α/β) by a new concept, the normal-tissue effective fractionation sensitivity, [Formula: see text], which takes into account both the dose heterogeneity in, and the volume effect of, the late-responding normal-tissue in question. Closed-form analytical expressions for [Formula: see text] ensuring exact normal-tissue iso-effect are derived for: (i) uniform dose, and (ii) arbitrary dose distributions with volume-effect parameter n = 1 from the normal-tissue dose-volume histogram. For arbitrary dose distributions and arbitrary n, a numerical solution for [Formula: see text] exhibits a weak dependence on the number of fractions. As n is increased, [Formula: see text] increases from its intrinsic value at n = 0 (100% serial normal-tissue) to values close to or even exceeding the tumour (α/β) at n = 1 (100% parallel normal-tissue), with the highest values of [Formula: see text] corresponding to the most conformal dose distributions. Applications of this new concept to inverse planning and to highly conformal modalities are discussed, as is the effect of possible deviations from LQ behaviour at large fraction sizes.

  9. Validation of putative reference genes for normalization of Q-RT-PCR data from paraffin-embedded lymphoid tissue

    DEFF Research Database (Denmark)

    Green, Tina Marie; de Stricker, Karin; Møller, Michael Boe

    2009-01-01

    Normalization of quantitative reverse transcription-PCR (Q-RT-PCR) data to appropriate tissue-specific reference genes is an essential part of interpreting the results. This study aimed to determine the most appropriate reference genes for normalizing gene expressions in lymphatic tissue...... was 0.93 (Pnormalization with the appropriate reference genes. Thus, we show that formalin-fixed, paraffin-embedded lymphoid samples are suitable for Q-RT-PCR when using thoroughly validated reference genes....

  10. Hypothyroidism after primary radiotherapy for head and neck squamous cell carcinoma: Normal tissue complication probability modeling with latent time correction

    DEFF Research Database (Denmark)

    Rønjom, Marianne Feen; Brink, Carsten; Bentzen, Søren

    2013-01-01

    To develop a normal tissue complication probability (NTCP) model of radiation-induced biochemical hypothyroidism (HT) after primary radiotherapy for head and neck squamous cell carcinoma (HNSCC) with adjustment for latency and clinical risk factors.......To develop a normal tissue complication probability (NTCP) model of radiation-induced biochemical hypothyroidism (HT) after primary radiotherapy for head and neck squamous cell carcinoma (HNSCC) with adjustment for latency and clinical risk factors....

  11. The functional state of perfused liver tissue in X-ray irradiated rats

    International Nuclear Information System (INIS)

    Borovikova, G.V.; Dokshina, G.A.; Lapteva, T.A.

    1981-01-01

    The results of studying the functional state of perfused liver tissue isolated from rates after irradiation in the 18.06x10 - 2 Kl/kg dose, which has been estimated by transamination process rate catalized alanine-(KF 2.6x1.2, ALT and aspartate by aminotransferases (KF 2.6x1.1, ACT), gluconeogenesis and urea production intensity presented. When comparing the results obtained on the perfused liver deprived of homeostatic body effects it has been found that the liver isolated from the body for the first 24 hours of the radiation sickness development possesses a higher radiation activity which manifests itself in intensification of the processes of gluconeogenesis and transamination with substrate addition. The third 24 hours upon irradiation in the isolated liver the intensity of the gluconeogenesis and transamination processes is attenuated

  12. Functional state of perfused liver tissue in X-ray irradiated rats

    Energy Technology Data Exchange (ETDEWEB)

    Borovikova, G.V.; Dokshina, G.A.; Lapteva, T.A. (Tomskij Gosudarstvennyj Univ. (USSR). Nauchno-Issledovatel' skij Inst. Biologii i Biofiziki)

    1981-01-01

    The results of studying the functional state of perfused liver tissue isolated from rats after irradiation in the 18.06x10/sup -2/ Kl/kg dose, which has been estimated by transamination process rate catalized alanine-(KF 2.6x1.2, ALT and aspartate by aminotransferases (KF 2.6x1.1, ACT), gluconeogenesis and urea production intensity presented. When comparing the results obtained on the perfused liver deprived of homeostatic body effects it has been found that the liver isolated from the body for the first 24 hours of the radiation sickness development possesses a higher radiation activity which manifests itself in intensification of the processes of gluconeogenesis and transamination with substrate addition. The third 24 hours upon irradiation in the isolated liver the intensity of the gluconeogenesis and transamination processes is attenuated.

  13. Comparative study of rabbit VX2 hepatic implantation tumor and normal liver tissue on magnetic resonance perfusion weighted imaging

    International Nuclear Information System (INIS)

    Jiao Zimei; Wang Xizhen; Wang Bin; Liu Feng; Li Haiqing; Sun Yequan; Dong Peng

    2012-01-01

    Objective: To investigate the value of magnetic resonance (MR) perfusion weighted imaging (PWI) in evaluating the blood perfusion of tumor by analyzing the features and indexes of PWI on rabbit VX2 hepatic implantation tumor and normal liver tissue. Methods: Twenty-four New Zealand White rabbits with VX2 carcinoma were established under direct surgical vision embedding tumor tissue. MR examination was performed at 21 days after the tumor implantation. The signal intensity -time curve of hepatic tumor and normal liver tissue were obtained. Mean time to enhance (MTE), negative enhancement integral (NEI), time to minimum (TM), maximum slope of decrease (MSD) and maximum slope of increase (MSI) were measured. Results: MTE, NEI, TM, MSD, and MSI of the normal liver tissue were 208.341±2.226 ms, 78.334±8.152, 24.059±1.927 ms, 38.221±2.443, and 15.389±2.526, respectively. MTE, NEI, TM, MSD, and MSI of the tumor tissue were 175.437±4.182 ms, 123.203±19.455, 17.061±1.834 ms, 125.740±4.842, and 67.832±2.882, respectively. The MTE and TM of tumor were shorter than those of normal hepatic tissue (P<0.05). NEI, MSD, and MSI of tumor were higher than those of normal hepatic tissue (P<0.05). Conclusion: PWI can distinguish the normal liver tissue from the tumor tissue, which is helpful in evaluating blood perfusion of different hepatic tissues. (authors)

  14. Effects on normal tissues during radiosensitization of Dalton's Lymphoma by the DNA ligand Hoechst 33342 in Balb/c mice

    International Nuclear Information System (INIS)

    Kalra, Namita; Sampath, Swapna; Adhikari, J.S.; Dwarakanath, B.S.

    2014-01-01

    Hoechst 33342 is a bisbenzimidazole derivative with AT specific minor groove DNA binding ability. Scavenging of free radicals and stabilization of macromolecular structure resulting in reduced induction of DNA damage contributes to radioprotection afforded by the ligand. Their ability to inhibit topoisomerases I and II, which play important roles in damage response pathways including DNA repair has been shown to sensitize tumor cells in vitro and in vivo. Due to its mutagenic and clastogenic potentials, damage to vital normal tissues are a matter of concern in deploying the ligand as adjuvant in radiotherapy. Therefore, we investigated the effects of the ligand in Dalton's Lymphoma (DL) bearing Balb/c mice by studying the local tumor control and animal survival, besides damage to normal tissues like bone marrow, kidney and testis. Hoechst 33342 (10 mg/kg b wt) was administered (i.v.) 1 h before focal irradiation (10 Gy) of the tumor (∼ 500 mm 3 ) grown on the hind leg of the mice. Partial response with a growth delay of 16 days (3 x initial volume) was seen following irradiation, while a complete response (cure; tumor-free survival) was observed in 88% mice following the combined treatment (Hoechst 33342+radiation); ligand alone had no significant effect. Although the ligand induced marginal degree of chromosomal aberrations in the bone marrow, it did not enhance aberrations induced by radiation further. In testes, the proportions of diploid, haploid and hypo-haploid cells as well as resting primary spermatocytes (RPS) were not significantly altered by either. In kidney, Hoechst 33342 alone or in combination with radiation did not cause significant damage to the proximal tubules and glomeruli. These observations suggest that radiosensitization of tumor by the DNA ligand Hoechst 33342 may not be associated with enhanced toxicity to bone marrow as well as proximal normal tissues. (author)

  15. The Contribution of Tissue Level Organization to Genomic Stability Following Low Dose/Low Dose Rate Gamma and Proton Irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Cheryl G. Burrell, Ph.D.

    2012-05-14

    The formation of functional tissue units is necessary in maintaining homeostasis within living systems, with individual cells contributing to these functional units through their three-dimensional organization with integrin and adhesion proteins to form a complex extra-cellular matrix (ECM). This is of particular importance in those tissues susceptible to radiation-induced tumor formation, such as epithelial glands. The assembly of epithelial cells of the thyroid is critical to their normal receipt of, and response to, incoming signals. Traditional tissue culture and live animals present significant challenges to radiation exposure and continuous sampling, however, the production of bioreactor-engineered tissues aims to bridge this gap by improve capabilities in continuous sampling from the same functional tissue, thereby increasing the ability to extrapolate changes induced by radiation to animals and humans in vivo. Our study proposes that the level of tissue organization will affect the induction and persistence of low dose radiation-induced genomic instability. Rat thyroid cells, grown in vitro as 3D tissue analogs in bioreactors and as 2D flask grown cultures were exposed to acute low dose (1, 5, 10 and 200 cGy) gamma rays. To assess immediate (6 hours) and delayed (up to 30 days) responses post-irradiation, various biological endpoints were studied including cytogenetic analyses, apoptosis analysis and cell viability/cytotoxicity analyses. Data assessing caspase 3/7 activity levels show that, this activity varies with time post radiation and that, overall, 3D cultures display more genomic instability (as shown by the lower levels of apoptosis over time) when compared to the 2D cultures. Variation in cell viability levels were only observed at the intermediate and late time points post radiation. Extensive analysis of chromosomal aberrations will give further insight on the whether the level of tissue organization influences genomic instability patterns after

  16. Study of electron densities of normal and neoplastic human breast tissues by Compton scattering using synchrotron radiation

    International Nuclear Information System (INIS)

    Antoniassi, M.; Conceição, A.L.C.; Poletti, M.E.

    2012-01-01

    Electron densities of 33 samples of normal (adipose and fibroglangular) and neoplastic (benign and malignant) human breast tissues were determined through Compton scattering data using a monochromatic synchrotron radiation source and an energy dispersive detector. The area of Compton peaks was used to determine the electron densities of the samples. Adipose tissue exhibits the lowest values of electron density whereas malignant tissue the highest. The relationship with their histology was discussed. Comparison with previous results showed differences smaller than 4%. - Highlights: ► Electron density of normal and neoplastic breast tissues was measured using Compton scattering. ► Monochromatic synchrotron radiation was used to obtain the Compton scattering data. ► The area of Compton peaks was used to determine the electron densities of samples. ► Adipose tissue shows the lowest electron density values whereas the malignant tissue the highest. ► Comparison with previous results showed differences smaller than 4%.

  17. Impact of Statistical Learning Methods on the Predictive Power of Multivariate Normal Tissue Complication Probability Models

    Energy Technology Data Exchange (ETDEWEB)

    Xu Chengjian, E-mail: c.j.xu@umcg.nl [Department of Radiation Oncology, University of Groningen, University Medical Center Groningen, Groningen (Netherlands); Schaaf, Arjen van der; Schilstra, Cornelis; Langendijk, Johannes A.; Veld, Aart A. van' t [Department of Radiation Oncology, University of Groningen, University Medical Center Groningen, Groningen (Netherlands)

    2012-03-15

    Purpose: To study the impact of different statistical learning methods on the prediction performance of multivariate normal tissue complication probability (NTCP) models. Methods and Materials: In this study, three learning methods, stepwise selection, least absolute shrinkage and selection operator (LASSO), and Bayesian model averaging (BMA), were used to build NTCP models of xerostomia following radiotherapy treatment for head and neck cancer. Performance of each learning method was evaluated by a repeated cross-validation scheme in order to obtain a fair comparison among methods. Results: It was found that the LASSO and BMA methods produced models with significantly better predictive power than that of the stepwise selection method. Furthermore, the LASSO method yields an easily interpretable model as the stepwise method does, in contrast to the less intuitive BMA method. Conclusions: The commonly used stepwise selection method, which is simple to execute, may be insufficient for NTCP modeling. The LASSO method is recommended.

  18. Impact of statistical learning methods on the predictive power of multivariate normal tissue complication probability models.

    Science.gov (United States)

    Xu, Cheng-Jian; van der Schaaf, Arjen; Schilstra, Cornelis; Langendijk, Johannes A; van't Veld, Aart A

    2012-03-15

    To study the impact of different statistical learning methods on the prediction performance of multivariate normal tissue complication probability (NTCP) models. In this study, three learning methods, stepwise selection, least absolute shrinkage and selection operator (LASSO), and Bayesian model averaging (BMA), were used to build NTCP models of xerostomia following radiotherapy treatment for head and neck cancer. Performance of each learning method was evaluated by a repeated cross-validation scheme in order to obtain a fair comparison among methods. It was found that the LASSO and BMA methods produced models with significantly better predictive power than that of the stepwise selection method. Furthermore, the LASSO method yields an easily interpretable model as the stepwise method does, in contrast to the less intuitive BMA method. The commonly used stepwise selection method, which is simple to execute, may be insufficient for NTCP modeling. The LASSO method is recommended. Copyright © 2012 Elsevier Inc. All rights reserved.

  19. Radiosensitization of tumors and normal tissues by combined treatment with misonidazole and heat

    International Nuclear Information System (INIS)

    Hofer, K.G.; MacKinnon, A.R.; Schubert, A.L.; Lehr, J.E.; Grimmett, E.V.

    1981-01-01

    Combination treatment of mice with misonidazole (0.5 mg/g body wt.) and hyperthermia (41.5/sup o/C for 45 mins.) produced dramatic radiosensitization in hypoxic BP-8 murine sarcoma cells. The dose modifying factor (DMF: 4.3) was such that hypoxic BP-8 cells subjected to combination therapy became more radiosensitive than untreated, fully oxygenated cell populations. In contrast, radiosensitization by combination treatment was comparatively minor or completely absent in normal body tissues such as skin (DMF: 1.57), intestine (DMF: 1.0), and bone marrow (DMF: 1.0). These results suggest that simultaneous administration of misonidazole and hyperthermia may prove an effective adjuvant to conventional clinical radiation therapy

  20. Photodynamic therapy in prostate cancer: optical dosimetry and response of normal tissue

    Science.gov (United States)

    Chen, Qun; Shetty, Sugandh D.; Heads, Larry; Bolin, Frank; Wilson, Brian C.; Patterson, Michael S.; Sirls, Larry T., II; Schultz, Daniel; Cerny, Joseph C.; Hetzel, Fred W.

    1993-06-01

    The present study explores the possibility of utilizing photodynamic therapy (PDT) in treating localized prostate carcinoma. Optical properties of ex vivo human prostatectomy specimens, and in vivo and ex vivo dog prostate glands were studied. The size of the PDT induced lesion in dog prostate was pathologically evaluated as a biological endpoint. The data indicate that the human normal and carcinoma prostate tissues have similar optical properties. The average effective attenuation depth is less in vivo than that of ex vivo. The PDT treatment generated a lesion size of up to 16 mm in diameter. The data suggest that PDT is a promising modality in prostate cancer treatment. Multiple fiber system may be required for clinical treatment.

  1. Rectification of pulsatile stress on soft tissues: a mechanism for normal-pressure hydrocephalus

    Science.gov (United States)

    Jalikop, Shreyas; Hilgenfeldt, Sascha

    2011-11-01

    Hydrocephalus is a pathological condition of the brain that occurs when cerebrospinal fluid (CSF) accumulates excessively in the brain cavities, resulting in compression of the brain parenchyma. Counter-intuitively, normal-pressure hydrocephalus (NPH) does not show elevated pressure differences across the compressed parenchyma. We investigate the effects of nonlinear tissue mechanics and periodic driving in this system. The latter is due to the cardiac cycle, which provides significant intracranial pressure and volume flow rate fluctuations. Nonlinear rectification of the periodic driving within a model of fluid flow in poroelastic material can lead to compression or expansion of the parenchyma, and this effect does not rely on changes in the mean intracranial pressure. The rectification effects can occur gradually over several days, in agreement with clinical studies of NPH.

  2. Differentiating fibroadenoma and ductal carcinoma in situ from normal breast tissue by multiphoton microscopy

    Science.gov (United States)

    Nie, Yuting; Wu, Yan; Lian, Yuane; Fu, Fangmeng; Wang, Chuan; Chen, Jianxin

    2014-09-01

    Fibroadenoma (FA) is the most common benign tumor of the female breast and several studies have reported that women with it have increased risk of breast cancer. While the ductal carcinoma in situ (DCIS) is a very early form of breast cancer. Thus, early detections of FA and DCIS are critical for improving breast tumor outcome and survival. In this paper, we use multiphoton microscopy (MPM) to obtain the high-contrast images of fresh, unfixed, unstained human breast specimens (normal breast tissue, FA and DCIS). Our results show that MPM has the ability to identify the characteristics of FA and DCIS including changes of duct architecture and collagen morphology. These results are consistent with the histological results. With the advancement of MPM, the technique has potential ability to serve as a real-time noninvasive imaging tool for early detection of breast tumor.

  3. Impact of Statistical Learning Methods on the Predictive Power of Multivariate Normal Tissue Complication Probability Models

    International Nuclear Information System (INIS)

    Xu Chengjian; Schaaf, Arjen van der; Schilstra, Cornelis; Langendijk, Johannes A.; Veld, Aart A. van’t

    2012-01-01

    Purpose: To study the impact of different statistical learning methods on the prediction performance of multivariate normal tissue complication probability (NTCP) models. Methods and Materials: In this study, three learning methods, stepwise selection, least absolute shrinkage and selection operator (LASSO), and Bayesian model averaging (BMA), were used to build NTCP models of xerostomia following radiotherapy treatment for head and neck cancer. Performance of each learning method was evaluated by a repeated cross-validation scheme in order to obtain a fair comparison among methods. Results: It was found that the LASSO and BMA methods produced models with significantly better predictive power than that of the stepwise selection method. Furthermore, the LASSO method yields an easily interpretable model as the stepwise method does, in contrast to the less intuitive BMA method. Conclusions: The commonly used stepwise selection method, which is simple to execute, may be insufficient for NTCP modeling. The LASSO method is recommended.

  4. Short- and Mid-term Effects of Irreversible Electroporation on Normal Renal Tissue: An Animal Model

    International Nuclear Information System (INIS)

    Wendler, J. J.; Porsch, M.; Hühne, S.; Baumunk, D.; Buhtz, P.; Fischbach, F.; Pech, M.; Mahnkopf, D.; Kropf, S.; Roessner, A.; Ricke, J.; Schostak, M.; Liehr, U.-B.

    2013-01-01

    Irreversible electroporation (IRE) is a novel nonthermal tissue ablation technique by high current application leading to apoptosis without affecting extracellular matrix. Previous results of renal IRE shall be supplemented by functional MRI and differentiated histological analysis of renal parenchyma in a chronic treatment setting. Three swine were treated with two to three multifocal percutaneous IRE of the right kidney. MRI was performed before, 30 min (immediate-term), 7 days (short-term), and 28 days (mid-term) after IRE. A statistical analysis of the lesion surrounded renal parenchyma intensities was made to analyze functional differences depending on renal part, side and posttreatment time. Histological follow-up of cortex and medulla was performed after 28 days. A total of eight ablations were created. MRI showed no collateral damage of surrounded tissue. The highest visual contrast between lesions and normal parenchyma was obtained by T2-HR-SPIR-TSE-w sequence of DCE-MRI. Ablation zones showed inhomogeneous necroses with small perifocal edema in the short-term and sharp delimitable scars in the mid-term. MRI showed no significant differences between adjoined renal parenchyma around ablations and parenchyma of untreated kidney. Histological analysis demonstrated complete destruction of cortical glomeruli and tubules, while collecting ducts, renal calyxes, and pelvis of medulla were preserved. Adjoined kidney parenchyma around IRE lesions showed no qualitative differences to normal parenchyma of untreated kidney. This porcine IRE study reveals a multifocal renal ablation, while protecting surrounded renal parenchyma and collecting system over a mid-term period. That offers prevention of renal function ablating centrally located or multifocal renal masses.

  5. Short- and Mid-term Effects of Irreversible Electroporation on Normal Renal Tissue: An Animal Model

    Energy Technology Data Exchange (ETDEWEB)

    Wendler, J. J., E-mail: johann.wendler@med.ovgu.de; Porsch, M.; Huehne, S.; Baumunk, D. [University of Magdeburg, Department of Urology (Germany); Buhtz, P. [Institute of Pathology, University of Magdeburg (Germany); Fischbach, F.; Pech, M. [University of Magdeburg, Department of Radiology (Germany); Mahnkopf, D. [Institute of Medical Technology and Research (Germany); Kropf, S. [Institute of Biometry, University of Magdeburg (Germany); Roessner, A. [Institute of Pathology, University of Magdeburg (Germany); Ricke, J. [University of Magdeburg, Department of Radiology (Germany); Schostak, M.; Liehr, U.-B. [University of Magdeburg, Department of Urology (Germany)

    2013-04-15

    Irreversible electroporation (IRE) is a novel nonthermal tissue ablation technique by high current application leading to apoptosis without affecting extracellular matrix. Previous results of renal IRE shall be supplemented by functional MRI and differentiated histological analysis of renal parenchyma in a chronic treatment setting. Three swine were treated with two to three multifocal percutaneous IRE of the right kidney. MRI was performed before, 30 min (immediate-term), 7 days (short-term), and 28 days (mid-term) after IRE. A statistical analysis of the lesion surrounded renal parenchyma intensities was made to analyze functional differences depending on renal part, side and posttreatment time. Histological follow-up of cortex and medulla was performed after 28 days. A total of eight ablations were created. MRI showed no collateral damage of surrounded tissue. The highest visual contrast between lesions and normal parenchyma was obtained by T2-HR-SPIR-TSE-w sequence of DCE-MRI. Ablation zones showed inhomogeneous necroses with small perifocal edema in the short-term and sharp delimitable scars in the mid-term. MRI showed no significant differences between adjoined renal parenchyma around ablations and parenchyma of untreated kidney. Histological analysis demonstrated complete destruction of cortical glomeruli and tubules, while collecting ducts, renal calyxes, and pelvis of medulla were preserved. Adjoined kidney parenchyma around IRE lesions showed no qualitative differences to normal parenchyma of untreated kidney. This porcine IRE study reveals a multifocal renal ablation, while protecting surrounded renal parenchyma and collecting system over a mid-term period. That offers prevention of renal function ablating centrally located or multifocal renal masses.